Neurotrophic factors in Alzheimer’s disease: role of axonal transport

Abstract

Neurotrophic factors (NTF) are small, versatile proteins that maintain survival and function to specific neuronal populations. In general, the axonal transport of NTF is important as not all of them are synthesized at the site of its action. Nerve growth factor (NGF), for instance, is produced in the neocortex and the hippocampus and then retrogradely transported to the cholinergic neurons of the basal forebrain. Neurodegenerative dementias like Alzheimer’s disease (AD) are linked to deficits in axonal transport. Furthermore, they are also associated with imbalanced distribution and dysregulation of NTF. In particular, brain‐derived neurotrophic factor (BDNF) plays a crucial role in cognition, learning and memory formation by modulating synaptic plasticity and is, therefore, a critical molecule in dementia and neurodegenerative diseases. Here, we review the changes of NTF expression and distribution (NGF, BDNF, neurotrophin‐3, neurotrophin‐4/5 and fibroblast growth factor‐2) and their receptors [tropomyosin‐related kinase (Trk)A, TrkB, TrkC and p75 NTR ] in AD and AD models. In addition, we focus on the interaction with neuropathological hallmarks Tau/neurofibrillary tangle and amyloid‐β (Abeta)/amyloid plaque pathology and their influence on axonal transport processes in order to unify AD‐specific cholinergic degeneration and Tau and Abeta misfolding through NTF pathophysiology.

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    Not in our library

89. 89.

    Kasa P, Rakonczay Z, Gulya K. The cholinergic system in Alzheimer’s disease. Prog Neurobiol. 1997;52:511-535.

    Not in our library10.1016/s0301-0082(97)00028-2

90. 90.

    Kato T, Sasaki H, Katagiri T, Sasaki H, Koiwai K, Youki H, Totsuka S, Ishii T. The binding of basic fibroblast growth factor to Alzheimer’s neurofibrillary tangles and senile plaques. Neurosci Lett. 1991;122:33-36.

    Not in our library10.1016/0304-3940(91)90186-w

91. 91.

    Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003;300:486-489.

    Not in our library10.1126/science.1079469

92. 92.

    Kerwin JM, Morris CM, Perry RH, Perry EK. Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer’s and Parkinson’s disease. Neurosci Lett. 1992;143:101-104.

    Not in our library10.1016/0304-3940(92)90242-y

93. 93.

    Kiprianova I, Schindowski K, von Bohlen und Halbach O, Krause S, Dono R, Schwaninger M, Unsicker K. Enlarged infarct volume and loss of BDNF mRNA induction following brain ischemia in mice lacking FGF-2. Exp Neurol. 2004;189:252-260.

    Not in our library10.1016/j.expneurol.2004.06.004

94. 94.

    Klenk J, Rapp K, Buchele G, Keil U, Weiland SK. Increasing life expectancy in Germany: quantitative contributions from changes in age- and disease-specific mortality. Eur J Public Health. 2007.

    Not in our library10.1093/eurpub/ckm024

95. 95.

    Kokubo H, Kayed R, Glabe CG, Yamaguchi H. Soluble Abeta oligomers ultrastructurally localize to cell processes and might be related to synaptic dysfunction in Alzheimer’s disease brain. Brain Res. 2005;1031:222-228.

    Not in our library10.1016/j.brainres.2004.10.041

96. 96.

    Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD. Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc Natl Acad Sci U S A. 2003;100:9980-9985.

    Not in our library10.1073/pnas.1533448100

97. 97.

    Kuner P, Hertel C. NGF induces apoptosis in a human neuroblastoma cell line expressing the neurotrophin receptor p75NTR. J Neurosci Res. 1998;54:465-474.

    Not in our library10.1002/(sici)1097-4547(19981115)54:4<465::aid-jnr4>3.0.co;2-t

98. 98.

    Kunugi H, Hattori M, Ueki A, Isse K, Hirasawa H, Nanko S. Possible association of missense mutation (Gly[-63]Glu) of the neurotrophin-3 gene with Alzheimer’s disease in Japanese. Neurosci Lett. 1998;241:65-67.

    Not in our library10.1016/s0304-3940(97)00953-1

99. 99.

    Kunugi H, Ueki A, Otsuka M, Isse K, Hirasawa H, Kato N, Nabika T, Kobayashi S, Nanko S. A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer’s disease. Mol Psychiatry. 2001;6:83-86.

    Not in our library10.1038/sj.mp.4000792

100. 100.

     Lang UE, Muhlbacher M, Hesselink MB, Zajaczkowski W, Danysz W, Danker-Hopfe H, Hellweg R. No nerve growth factor response to treatment with memantine in adult rats. J Neural Transm. 2004;111:181-190.

     Not in our library10.1007/s00702-003-0090-y

101. 101.

     Lazarov O, Lee M, Peterson DA, Sisodia SS. Evidence that synaptically released beta-amyloid accumulates as extracellular deposits in the hippocampus of transgenic mice. J Neurosci. 2002;22:9785-9793.

     Not in our library10.1523/jneurosci.22-22-09785.2002

102. 102.

     Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell. 2005;120:701-713.

     Not in our library10.1016/j.cell.2005.01.015

103. 103.

     Lee EB, Zhang B, Liu K, Greenbaum EA, Doms RW, Trojanowski JQ, Lee VM. BACE overexpression alters the subcellular processing of APP and inhibits Ab deposition in vivo. J Cell Biol. 2005a;168:291-302.

     Not in our library10.1083/jcb.200407070

104. 104.

     Lee J, Fukumoto H, Orne J, Klucken J, Raju S, Vanderburg CR, Irizarry MC, Hyman BT, Ingelsson M. Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms. Exp Neurol. 2005b;194:91-96.

     Not in our library10.1016/j.expneurol.2005.01.026

105. 105.

     Lesné S, Gabriel C, Nelson DA, White E, Mackenzie ET, Vivien D, Buisson A. Akt-dependent expression of NAIP-1 protects neurons against amyloid-β toxicity. J Biol Chem. 2005;280:24941-24947.

     Not in our library10.1074/jbc.m413495200

106. 106.

     Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M, Gwinn-Hardy K, Paul Murphy M, Baker M, Yu X, Duff K, Hardy J, Corral A, Lin WL, Yen SH, Dickson DW, Davies P, Hutton M. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet. 2000;25:402-405.

     Not in our library10.1038/78078

107. 107.

     Li Y, Rowland C, Tacey K, Catanese J, Sninsky J, Hardy J, Powell J, Lovestone S, Morris JC, Thal L, Goate A, Owen M, Williams J, Grupe A. The BDNF Val66Met polymorphism is not associated with late onset Alzheimer’s disease in three case-control samples. Mol Psychiatry. 2005;10:809-810.

     Not in our library10.1038/sj.mp.4001702

108. 108.

     Loy R, Heyer D, Clagett-Dame M, DiStefano PS. Localization of NGF receptors in normal and Alzheimer’s basal forebrain with monoclonal antibodies against the truncated form of the receptor. J Neurosci Res. 1990;27:651-664.

     Not in our library10.1002/jnr.490270426

109. 109.

     Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol. 1999;155:853-862.

     Not in our library10.1016/s0002-9440(10)65184-x

110. 110.

     Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci U S A. 2006;103:5644-5651.

     Not in our library10.1073/pnas.0600549103

111. 111.

     Mai L, Jope RS, Li X. BDNF-mediated signal transduction is modulated by GSK3beta and mood stabilizing agents. J Neurochem. 2002;82:75-83.

     Not in our library10.1046/j.1471-4159.2002.00939.x

112. 112.

     Maloney MT, Minamide LS, Kinley AW, Boyle JA, Bamburg JR. Beta-secretase-cleaved amyloid precursor protein accumulates at actin inclusions induced in neurons by stress or amyloid beta: a feedforward mechanism for Alzheimer’s disease. J Neurosci. 2005;25:11313-11321.

     Not in our library10.1523/jneurosci.3711-05.2005

113. 113.

     Mandelkow EM, Thies E, Trinczek B, Biernat J, Mandelkow E. MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. J Cell Biol. 2004;167:99-110.

     Not in our library10.1083/jcb.200401085

114. 114.

     Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry. 1999;46:929-940.

     Not in our library10.1016/s0006-3223(99)00165-1

115. 115.

     Marvanova M, Lakso M, Pirhonen J, Nawa H, Wong G, Castren E. The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci. 2001;18:247-258.

     Not in our library10.1006/mcne.2001.1027

116. 116.

     Matsushita S, Arai H, Matsui T, Yuzuriha T, Urakami K, Masaki T, Higuchi S. Brain-derived neurotrophic factor gene polymorphisms and Alzheimer’s disease. J Neural Transm. 2005;112:703-711.

     Not in our library10.1007/s00702-004-0210-3

117. 117.

     Michalski B, Fahnestock M. Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer’s disease. Brain Res Mol Brain Res. 2003;111:148-154.

     Not in our library10.1016/s0169-328x(03)00003-2

118. 118.

     Mobley WC, Neve RL, Prusiner SB, McKinley MP. Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain. Proc Natl Acad Sci U S A. 1988;85:9811-9815.

     Not in our library10.1073/pnas.85.24.9811

119. 119.

     Mudher A, Shepherd D, Newman TA, Mildren P, Jukes JP, Squire A, Mears A, Drummond JA, Berg S, MacKay D, Asuni AA, Bhat R, Lovestone S. GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol Psychiatry. 2004;9:522-530.

     Not in our library10.1038/sj.mp.4001483

120. 120.

     Mufson EJ, Conner JM, Kordower JH. Nerve growth factor in Alzheimer’s disease: defective retrograde transport to nucleus basalis. Neuroreport. 1995;6:1063-1066.

     Not in our library10.1097/00001756-199505090-00028

121. 121.

     Mufson EJ, Lavine N, Jaffar S, Kordower JH, Quirion R, Saragovi HU. Reduction in p140-TrkA receptor protein within the nucleus basalis and cortex in Alzheimer’s disease. Exp Neurol. 1997;146:91-103.

     Not in our library10.1006/exnr.1997.6504

122. 122.

     Mufson EJ, Ma SY, Cochran EJ, Bennett DA, Beckett LA, Jaffar S, Saragovi HU, Kordower JH. Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer’s disease. J Comp Neurol. 2000;427:19-30.

     Not in our library10.1002/1096-9861(20001106)427:1<19::aid-cne2>3.0.co;2-a

123. 123.

     Mufson EJ, Ma SY, Dills J, Cochran EJ, Leurgans S, Wuu J, Bennett DA, Jaffar S, Gilmor ML, Levey AI, Kordower JH. Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer’s disease. J Comp Neurol. 2002;443:136-153.

     Not in our library10.1002/cne.10122

124. 124.

     Mufson EJ, Ginsberg SD, Ikonomovic MD, DeKosky ST. Human cholinergic basal forebrain: chemoanatomy and neurologic dysfunction. J Chem Neuroanat. 2003;26:233-242.

     Not in our library10.1016/s0891-0618(03)00068-1

125. 125.

     Murase K, Igarashi K, Hayashi K. Neurotrophin-3 (NT-3) levels in the developing rat nervous system and in human samples. Clin Chim Acta. 1994;227:23-36.

     Not in our library10.1016/0009-8981(94)90132-5

126. 126.

     Murer MG, Boissiere F, Yan Q, Hunot S, Villares J, Faucheux B, Agid Y, Hirsch E, Raisman-Vozari R. An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer’s disease. Neuroscience. 1999;88:1015-1032.

     Not in our library10.1016/s0306-4522(98)00219-x

127. 127.

     Murer MG, Yan Q, Raisman-Vozari R. Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease. Prog Neurobiol. 2001;63:71-124.

     Not in our library10.1016/s0301-0082(00)00014-9

128. 128.

     Muresan Z, Muresan V. Neuritic deposits of amyloid-b peptide in a subpopulation of central nervous system-derived neuronal cells. Mol Cell Biol. 2006;26:4982-4997.

     Not in our library10.1128/mcb.00371-06

129. 129.

     Nacmias B, Piccini C, Bagnoli S, Tedde A, Cellini E, Bracco L, Sorbi S. Brain-derived neurotrophic factor, apolipoprotein E genetic variants and cognitive performance in Alzheimer’s disease. Neurosci Lett. 2004;367:379-383.

     Not in our library10.1016/j.neulet.2004.06.039

130. 130.

     Narisawa-Saito M, Wakabayashi K, Tsuji S, Takahashi H, Nawa H. Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer’s disease. Neuroreport. 1996;7:2925-2928.

     Not in our library10.1097/00001756-199611250-00024

131. 131.

     Nishimura M, Kuno S, Kaji R, Kawakami H. Brain-derived neurotrophic factor gene polymorphisms in Japanese patients with sporadic Alzheimer’s disease, Parkinson’s disease, and multiple system atrophy. Mov Disord. 2005;20:1031-1033.

     Not in our library10.1002/mds.20491

132. 132.

     Nuydens R, Dispersyn G, de Jong M, van den Kieboom G, Borgers M, Geerts H. Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells. Biochem Biophys Res Commun. 1997;240:687-691.

     Not in our library10.1006/bbrc.1997.7721

133. 133.

     Olin D, MacMurray J, Comings DE. Risk of late-onset Alzheimer’s disease associated with BDNF C270T polymorphism. Neurosci Lett. 2005;381:275-278.

     Not in our library10.1016/j.neulet.2005.02.017

134. 134.

     Olivieri G, Novakovic M, Savaskan E, Meier F, Baysang G, Brockhaus M, Muller-Spahn F. The effects of beta-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and beta-amyloid secretion. Neuroscience. 2002;113:849-855.

     Not in our library10.1016/s0306-4522(02)00211-7

135. 135.

     Olivieri G, Otten U, Meier F, Baysang G, Dimitriades-Schmutz B, Muller-Spahn F, Savaskan E. Beta-amyloid modulates tyrosine kinase B receptor expression in SHSY5Y neuroblastoma cells: influence of the antioxidant melatonin. Neuroscience. 2003;120:659-665.

     Not in our library10.1016/s0306-4522(03)00342-7

136. 136.

     Origlia N, Capsoni S, Domenici L, Cattaneo A. Time window in cholinomimetic ability to rescue long-term potentiation in neurodegenerating anti-nerve growth factor mice. J Alzheimers Dis. 2006;9:59-68.

     Not in our library10.3233/jad-2006-9106

137. 137.

     Patapoutian A, Reichardt LF. Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol. 2001;11:272-280.

     Not in our library10.1016/s0959-4388(00)00208-7

138. 138.

     Peng S, Wuu J, Mufson EJ, Fahnestock M. Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol. 2004;63:641-649.

     Not in our library10.1093/jnen/63.6.641

139. 139.

     Peng S, Wuu J, Mufson EJ, Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem. 2005;93:1412-1421.

     Not in our library10.1111/j.1471-4159.2005.03135.x

140. 140.

     Perry EK, Johnson M, Kerwin JM, Piggott MA, Court JA, Shaw PJ, Ince PG, Brown A, Perry RH. Convergent cholinergic activities in aging and Alzheimer’s disease. Neurobiol Aging. 1992;13:393-400.

     Not in our library10.1016/0197-4580(92)90113-c

141. 141.

     Perry EK, Irving D, Kerwin JM, McKeith IG, Thompson P, Collerton D, Fairbairn AF, Ince PG, Morris CM, Cheng AV, Perry RH. Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson’s and distinction from Alzheimer disease. Alzheimer Dis Assoc Disord. 1993;7:69-79.

     Not in our library10.1097/00002093-199307020-00002

142. 142.

     Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron. 1991;7:695-702.

     Not in our library10.1016/0896-6273(91)90273-3

143. 143.

     Pike CJ, Cummings BJ, Monzavi R, Cotman CW. Beta-amyloid-induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzheimer’s disease. Neuroscience. 1994;63:517-531.

     Not in our library10.1016/0306-4522(94)90547-9

144. 144.

     Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinisto L, Halonen P, Kontula K. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. N Engl J Med. 1995;333:1242-1247.

     Not in our library10.1056/nejm199511093331902

145. 145.

     Probst A, Gotz J, Wiederhold KH, Tolnay M, Mistl C, Jaton AL, Hong M, Ishihara T, Lee VM, Trojanowski JQ, Jakes R, Crowther RA, Spillantini MG, Burki K, Goedert M. Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol (Berl). 2000;99:469-481.

     Not in our library10.1007/s004010051148

146. 146.

     Qiu Z, Naten DL, Liston JC, Yess J, Rebeck GW. A novel approach for studying endogenous ab processing using cultured primary neurons isolated from APP transgenic mice. Exp Neurol. 2001;170:186-194.

     Not in our library10.1006/exnr.2001.7703

147. 147.

     Riemenschneider M, Schwarz S, Wagenpfeil S, Diehl J, Muller U, Forstl H, Kurz A. A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer’s disease in patients lacking the Apolipoprotein E epsilon4 allele. Mol Psychiatry. 2002;7:782-785.

     Not in our library10.1038/sj.mp.4001073

148. 148.

     Robakis NK, Anderson JP, Refolo LM, Wallace W. Expression of the Alzheimer amyloid precursor in brain tissue and effects of NGF and EGF on its metabolism. Clin Neuropharmacol. 1991;14(Suppl. 1):S15-S23.

     Not in our library10.1097/00002826-199114001-00004

149. 149.

     Rossner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V. p75 and TrkA receptor signaling independently regulate amyloid precursor protein mRNA expression, isoform composition, and protein secretion in PC12 cells. J Neurochem. 1998;71:757-766.

     Not in our library10.1046/j.1471-4159.1998.71020757.x

150. 150.

     Ruiz-Leon Y, Pascual A. Regulation of beta-amyloid precursor protein expression by brain-derived neurotrophic factor involves activation of both the Ras and phosphatidylinositide 3-kinase signalling pathways. J Neurochem. 2004;88:1010-1018.

     Not in our library10.1046/j.1471-4159.2003.02226.x

151. 151.

     Saarela MS, Lehtimaki T, Rinne JO, Huhtala H, Rontu R, Hervonen A, Roytta M, Ahonen JP, Mattila KM. No association between the brain-derived neurotrophic factor 196 G>A or 270 C>T polymorphisms and Alzheimer’s or Parkinson’s disease. Folia Neuropathol. 2006;44:12-16.

     Not in our library

152. 152.

     Sadot E, Heicklen-Klein A, Barg J, Lazarovici P, Ginzburg I. Identification of a tau promoter region mediating tissue-specific-regulated expression in PC12 cells. J Mol Biol. 1996;256:805-812.

     Not in our library10.1006/jmbi.1996.0126

153. 153.

     Saez ET, Pehar M, Vargas MR, Barbeito L, Maccioni RB. Production of nerve growth factor by beta-amyloid-stimulated astrocytes induces p75(NTR)-dependent tau hyperphosphorylation in cultured hippocampal neurons. J Neurosci Res. 2006;84:1098-1106.

     Not in our library10.1002/jnr.20996

154. 154.

     Salehi A, Verhaagen J, Dijkhuizen PA, Swaab DF. Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer’s disease. Neuroscience. 1996;75:373-387.

     Not in our library10.1016/0306-4522(96)00273-4

155. 155.

     Salehi A, Ocampo M, Verhaagen J, Swaab DF. P75 neurotrophin receptor in the nucleus basalis of meynert in relation to age, sex, and Alzheimer’s disease. Exp Neurol. 2000;161:245-258.

     Not in our library10.1006/exnr.1999.7252

156. 156.

     Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Goldstein LS, Mobley WC. Increased App expression in a mouse model of Down’s syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron. 2006;51:29-42.

     Not in our library10.1016/j.neuron.2006.05.022

157. 157.

     Savaskan E, Muller-Spahn F, Olivieri G, Bruttel S, Otten U, Rosenberg C, Hulette C, Hock C. Alterations in trk A, trk B and trk C receptor immunoreactivities in parietal cortex and cerebellum in Alzheimer’s disease. Eur Neurol. 2000;44:172-180.

     Not in our library10.1159/000008229

158. 158.

     Scott SA, Mufson EJ, Weingartner JA, Skau KA, Crutcher KA. Nerve growth factor in Alzheimer’s disease: increased levels throughout the brain coupled with declines in nucleus basalis. J Neurosci. 1995;15:6213-6221.

     Not in our library10.1523/jneurosci.15-09-06213.1995

159. 159.

     Seitz A, Kojima H, Oiwa K, Mandelkow EM, Song YH, Mandelkow E. Single-molecule investigation of the interference between kinesin, tau and MAP2c. EMBO J. 2002;21:4896-4905.

     Not in our library10.1093/emboj/cdf503

160. 160.

     Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741-766.

     Not in our library10.1152/physrev.2001.81.2.741

161. 161.

     Sergeant N, Delacourte A, Buee L. Tau protein as a differential biomarker of tauopathies. Biochim Biophys Acta. 2005;1739:179-197.

     Not in our library10.1016/j.bbadis.2004.06.020

162. 162.

     Shelton SB, Johnson GV. Tau and HMW tau phosphorylation and compartmentalization in apoptotic neuronal PC12 cells. J Neurosci Res. 2001;66:203-213.

     Not in our library10.1002/jnr.1212

163. 163.

     Shen ZX. Brain cholinesterases: III. Future perspectives of AD research and clinical practice. Med Hypotheses. 2004;63:298-307.

     Not in our library10.1016/j.mehy.2004.03.001

164. 164.

     Sheng JG, Price DL, Koliatsos VE. Disruption of corticocortical connections ameliorates amyloid burden in terminal fields in a transgenic model of Ab amyloidosis. J Neurosci. 2002;22:9794-9799.

     Not in our library10.1523/jneurosci.22-22-09794.2002

165. 165.

     Siedlak SL, Cras P, Kawai M, Richey P, Perry G. Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease. J Histochem Cytochem. 1991;39:899-904.

     Not in our library10.1177/39.7.1865106

166. 166.

     Siegel GJ, Chauhan NB. Neurotrophic factors in Alzheimer’s and Parkinson’s disease brain. Brain Res Brain Res Rev. 2000;33:199-227.

     Not in our library10.1016/s0165-0173(00)00030-8

167. 167.

     Sokol DK, Chen D, Farlow MR, Dunn DW, Maloney B, Zimmer JA, Lahiri DK. High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression. J Child Neurol. 2006;21:444-449.

     Not in our library10.1177/08830738060210062201

168. 168.

     Soto I, Rosenthal JJ, Blagburn JM, Blanco RE. Fibroblast growth factor 2 applied to the optic nerve after axotomy up-regulates BDNF and TrkB in ganglion cells by activating the ERK and PKA signaling pathways. J Neurochem. 2006;96:82-96.

     Not in our library10.1111/j.1471-4159.2005.03510.x

169. 169.

     Stamer K, Vogel R, Thies E, Mandelkow E, Mandelkow EM. Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J Cell Biol. 2002;156:1051-1063.

     Not in our library10.1083/jcb.200108057

170. 170.

     Stieber A, Mourelatos Z, Gonatas NK. In Alzheimer’s disease the Golgi apparatus of a population of neurons without neurofibrillary tangles is fragmented and atrophic. Am J Pathol. 1996;148:415-426.

     Not in our library

171. 171.

     Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science. 2005;307:1282-1288.

     Not in our library10.1126/science.1105681

172. 172.

     Svendsen CN, Cooper JD, Sofroniew MV. Trophic factor effects on septal cholinergic neurons. Ann N Y Acad Sci. 1991;640:91-94.

     Not in our library10.1111/j.1749-6632.1991.tb00197.x

173. 173.

     Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, Gouras GK. Oligomerization of Alzheimer’s beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci. 2004;24:3592-3599.

     Not in our library10.1523/jneurosci.5167-03.2004

174. 174.

     Takami K, Matsuo A, Terai K, Walker DG, McGeer EG, McGeer PL. Fibroblast growth factor receptor-1 expression in the cortex and hippocampus in Alzheimer’s disease. Brain Res. 1998;802:89-97.

     Not in our library10.1016/s0006-8993(98)00552-6

175. 175.

     Tatebayashi Y, Iqbal K, Grundke-Iqbal I. Dynamic regulation of expression and phosphorylation of tau by fibroblast growth factor-2 in neural progenitor cells from adult rat hippocampus. J Neurosci. 1999;19:5245-5254.

     Not in our library10.1523/jneurosci.19-13-05245.1999

176. 176.

     Tatebayashi Y, Lee MH, Li L, Iqbal K, Grundke-Iqbal I. The dentate gyrus neurogenesis: a therapeutic target for Alzheimer’s disease. Acta Neuropathol (Berl). 2003;105:225-232.

     Not in our library10.1007/s00401-002-0636-3

177. 177.

     Tatebayashi Y, Haque N, Tung YC, Iqbal K, Grundke-Iqbal I. Role of tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport. J Cell Sci. 2004;117:1653-1663.

     Not in our library10.1242/jcs.01018

178. 178.

     Thoenen H, Zafra F, Hengerer B, Lindholm D. The synthesis of nerve growth factor and brain-derived neurotrophic factor in hippocampal and cortical neurons is regulated by specific transmitter systems. Ann N Y Acad Sci. 1991;640:86-90.

     Not in our library10.1111/j.1749-6632.1991.tb00196.x

179. 179.

     Tong L, Shen H, Perreau VM, Balazs R, Cotman CW. Effects of exercise on gene-expression profile in the rat hippocampus. Neurobiol Dis. 2001a;8:1046-1056.

     Not in our library10.1006/nbdi.2001.0427

180. 180.

     Tong L, Thornton PL, Balazs R, Cotman CW. Beta-amyloid-(1-42) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival is not compromised. J Biol Chem. 2001b;276:17301-17306.

     Not in our library10.1074/jbc.m010450200

181. 181.

     Tong L, Balazs R, Thornton PL, Cotman CW. Beta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. J Neurosci. 2004;24:6799-6809.

     Not in our library10.1523/jneurosci.5463-03.2004

182. 182.

     Treanor JJ, Dawbarn D, Allen SJ, MacGowan SH, Wilcock GK. Low affinity nerve growth factor receptor binding in normal and Alzheimer’s disease basal forebrain. Neurosci Lett. 1991;121:73-76.

     Not in our library10.1016/0304-3940(91)90652-a

183. 183.

     Tsai J, Grutzendler J, Duff K, Gan WB. Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nat Neurosci. 2004a;7:1181-1183.

     Not in our library10.1038/nn1335

184. 184.

     Tsai SJ, Hong CJ, Liu HC, Liu TY, Hsu LE, Lin CH. Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms with Alzheimer’s disease and age of onset. Neuropsychobiology. 2004b;49:10-12.

     Not in our library10.1159/000075332

185. 185.

     Tsai SJ, Hong CJ, Liu HC, Liu TY, Liou YJ. The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer’s disease in a Chinese population. Dement Geriatr Cogn Disord. 2006;21:139-143.

     Not in our library10.1159/000090673

186. 186.

     Tsukamoto E, Hashimoto Y, Kanekura K, Niikura T, Aiso S, Nishimoto I. Characterization of the toxic mechanism triggered by Alzheimer’s amyloid-beta peptides via p75 neurotrophin receptor in neuronal hybrid cells. J Neurosci Res. 2003;73:627-636.

     Not in our library10.1002/jnr.10703

187. 187.

     Tuszynski MH, Smith DE, Roberts J, McKay H, Mufson E. Targeted intraparenchymal delivery of human NGF by gene transfer to the primate basal forebrain for 3 months does not accelerate beta-amyloid plaque deposition. Exp Neurol. 1998;154:573-582.

     Not in our library10.1006/exnr.1998.6956

188. 188.

     Tuszynski MH, Thal L, Pay M, Salmon DP, U HS, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G, Potkin SG, Fallon J, Hansen L, Mufson EJ, Kordower JH, Gall C, Conner J. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med. 2005;11:551-555.

     Not in our library10.1038/nm1239

189. 189.

     Venero JL, Knusel B, Beck KD, Hefti F. Expression of neurotrophin and trk receptor genes in adult rats with fimbria transections: effect of intraventricular nerve growth factor and brain-derived neurotrophic factor administration. Neuroscience. 1994;59:797-815.

     Not in our library10.1016/0306-4522(94)90285-2

190. 190.

     Vepsalainen S, Castren E, Helisalmi S, Iivonen S, Mannermaa A, Lehtovirta M, Hanninen T, Soininen H, Hiltunen M. Genetic analysis of BDNF and TrkB gene polymorphisms in Alzheimer’s disease. J Neurol. 2005;252:423-428.

     Not in our library10.1007/s00415-005-0667-5

191. 191.

     Verdile G, Fuller S, Atwood CS, Laws SM, Gandy SE, Martins RN. The role of beta amyloid in Alzheimer’s disease: still a cause of everything or the only one who got caught? Pharmacol Res. 2004;50:397-409.

     Not in our library10.1016/j.phrs.2003.12.028

192. 192.

     Villa A, Latasa MJ, Pascual A. Nerve growth factor modulates the expression and secretion of beta-amyloid precursor protein through different mechanisms in PC12 cells. J Neurochem. 2001;77:1077-1084.

     Not in our library10.1046/j.1471-4159.2001.00315.x

193. 193.

     Wirths O, Weis J, Kayed R, Saido TC, Bayer TA. Age-dependent axonal degeneration in an Alzheimer mouse model. Neurobiol Aging. 2006;8:1689-1699.

     Not in our library10.1016/j.neurobiolaging.2006.07.021

194. 194.

     Wolf SA, Kronenberg G, Lehmann K, Blankenship A, Overall R, Staufenbiel M, Kempermann G. Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer’s disease. Biol Psychiatry. 2006;60:1314-1323.

     Not in our library10.1016/j.biopsych.2006.04.004

195. 195.

     Wolfe MS, Kopan R. Intramembrane proteolysis: theme and variations. Science. 2004;305:1119-1123.

     Not in our library10.1126/science.1096187

196. 196.

     Wynn ZJ, Cummings JL. Cholinesterase inhibitor therapies and neuropsychiatric manifestations of Alzheimer’s disease. Dement Geriatr Cogn Disord. 2004;17:100-108.

     Not in our library10.1159/000074281

197. 197.

     Yamada T, Yoshiyama Y, Kawaguchi N. Expression of activating transcription factor-2 (ATF-2), one of the cyclic AMP response element (CRE) binding proteins, in Alzheimer disease and non-neurological brain tissues. Brain Res. 1997;749:329-334.

     Not in our library10.1016/s0006-8993(96)01356-x

198. 198.

     Yamamoto-Sasaki M, Ozawa H, Saito T, Rosler M, Riederer P. Impaired phosphorylation of cyclic AMP response element binding protein in the hippocampus of dementia of the Alzheimer type. Brain Res. 1999;824:300-303.

     Not in our library10.1016/s0006-8993(99)01220-2

199. 199.

     Yankner BA, Caceres A, Duffy LK. Nerve growth factor potentiates the neurotoxicity of beta amyloid. Proc Natl Acad Sci U S A. 1990;87:9020-9023.

     Not in our library10.1073/pnas.87.22.9020

Cited by papers we hold 9

• Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression · 2023
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• Combination Drug Therapy for the Management of Alzheimer’s Disease · 2020
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• Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy · 2019
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• Inhibition of NMDA Receptors Prevents the Loss of BDNF Function Induced by Amyloid β · 2018
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• Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches · 2018
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• Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease · 2015
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• Tau Protein Modifications and Interactions: Their Role in Function and Dysfunction · 2014
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• A Large, Cross-Sectional Observational Study of Serum BDNF, Cognitive Function, and Mild Cognitive Impairment in the Elderly · 2014
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• TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders · 2013
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