Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jan 15, 1992; 89(2): 569–573.

Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease.


Using a monoclonal antibody directed against the primate nerve growth factor (NGF) receptor, we examined the expression of NGF receptors within neuronal perikarya of normal adult human cerebral cortex (27-98 years old) and individuals with Alzheimer disease (AD). This expression of cortical NGF receptors was compared with that seen in other neurological diseases and normal human development as well as in young and aged nonhuman primates. NGF receptor-containing cortical neurons were not observed in young adults (less than 50 years old) and were observed only infrequently in non-demented elderly individuals (50-80 years old). In contrast, numerous NGF receptor-containing cortical neurons were seen in AD patients of all ages and in one 98-year-old nondemented patient. In advanced age and AD, numerous NGF receptor-positive neurons were located within laminae II-VI of temporal association cortices whereas only a few were seen in the subicular complex, entorhinal cortex, parahippocampal gyrus, and amygdaloid complex. These perikarya appeared healthy, with bipolar, fusiform, or multipolar morphologies and extended varicose dendritic arbors. These neurons failed to express neurofibrillary tangle-bearing material. In contrast to AD, NGF receptor-containing cortical neurons were not observed in Parkinson disease, Pick disease, or Shy-Drager syndrome. The NGF receptor-containing cortical neurons seen in advanced age and AD were similar in morphology to those observed in human fetal cortex. No NGF receptor-containing cortical neurons were observed in young or aged nonhuman primates. These findings suggest that neurons within the human cerebral cortex exhibit plasticity in their expression of NGF receptors in AD and extreme advanced aging.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Buell SJ, Coleman PD. Dendritic growth in the aged human brain and failure of growth in senile dementia. Science. 1979 Nov 16;206(4420):854–856. [PubMed]
  • Geddes JW, Monaghan DT, Cotman CW, Lott IT, Kim RC, Chui HC. Plasticity of hippocampal circuitry in Alzheimer's disease. Science. 1985 Dec 6;230(4730):1179–1181. [PubMed]
  • Chan-Palay V. Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer's and Parkinson's disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol. 1988 Jul 22;273(4):543–557. [PubMed]
  • Whittemore SR, Seiger A. The expression, localization and functional significance of beta-nerve growth factor in the central nervous system. Brain Res. 1987 Nov;434(4):439–464. [PubMed]
  • Hefti F, Hartikka J, Knusel B. Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases. Neurobiol Aging. 1989 Sep-Oct;10(5):515–533. [PubMed]
  • Mufson EJ, Bothwell M, Kordower JH. Loss of nerve growth factor receptor-containing neurons in Alzheimer's disease: a quantitative analysis across subregions of the basal forebrain. Exp Neurol. 1989 Sep;105(3):221–232. [PubMed]
  • Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science. 1982 Mar 5;215(4537):1237–1239. [PubMed]
  • Taniuchi M, Clark HB, Johnson EM., Jr Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4094–4098. [PMC free article] [PubMed]
  • Richardson PM, Issa VM, Riopelle RJ. Distribution of neuronal receptors for nerve growth factor in the rat. J Neurosci. 1986 Aug;6(8):2312–2321. [PubMed]
  • Banerjee SP, Snyder SH, Cuatrecasas P, Greene LA. Binding of nerve growth factor receptor in sympathetic ganglia. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2519–2523. [PMC free article] [PubMed]
  • Hefti F, Mash DC. Localization of nerve growth factor receptors in the normal human brain and in Alzheimer's disease. Neurobiol Aging. 1989 Jan-Feb;10(1):75–87. [PubMed]
  • Kordower JH, Bartus RT, Bothwell M, Schatteman G, Gash DM. Nerve growth factor receptor immunoreactivity in the nonhuman primate (Cebus apella): distribution, morphology, and colocalization with cholinergic enzymes. J Comp Neurol. 1988 Nov 22;277(4):465–486. [PubMed]
  • Mufson EJ, Bothwell M, Hersh LB, Kordower JH. Nerve growth factor receptor immunoreactive profiles in the normal, aged human basal forebrain: colocalization with cholinergic neurons. J Comp Neurol. 1989 Jul 8;285(2):196–217. [PubMed]
  • Kordower JH, Mufson EJ. Galanin-like immunoreactivity within the primate basal forebrain: differential staining patterns between humans and monkeys. J Comp Neurol. 1990 Apr 8;294(2):281–292. [PubMed]
  • Hefti F. Is Alzheimer disease caused by lack of nerve growth factor? Ann Neurol. 1983 Jan;13(1):109–110. [PubMed]
  • Mufson EJ, Higgins GA, Kordower JH. Nerve growth factor receptor immunoreactivity in the new world monkey (Cebus apella) and human cerebellum. J Comp Neurol. 1991 Jun 22;308(4):555–575. [PubMed]
  • Johnson EM, Jr, Taniuchi M, Clark HB, Springer JE, Koh S, Tayrien MW, Loy R. Demonstration of the retrograde transport of nerve growth factor receptor in the peripheral and central nervous system. J Neurosci. 1987 Mar;7(3):923–929. [PubMed]
  • Yan Q, Johnson EM., Jr An immunohistochemical study of the nerve growth factor receptor in developing rats. J Neurosci. 1988 Sep;8(9):3481–3498. [PubMed]
  • Yan Q, Clark HB, Johnson EM., Jr Nerve growth factor receptor in neural lobe of rat pituitary gland: immunohistochemical localization, biochemical characterization and regulation. J Neurocytol. 1990 Jun;19(3):302–312. [PubMed]
  • Allendoerfer KL, Shelton DL, Shooter EM, Shatz CJ. Nerve growth factor receptor immunoreactivity is transiently associated with the subplate neurons of the mammalian cerebral cortex. Proc Natl Acad Sci U S A. 1990 Jan;87(1):187–190. [PMC free article] [PubMed]
  • Koh S, Loy R. Localization and development of nerve growth factor-sensitive rat basal forebrain neurons and their afferent projections to hippocampus and neocortex. J Neurosci. 1989 Sep;9(9):2999–0318. [PubMed]
  • Higgins GA, Koh S, Chen KS, Gage FH. NGF induction of NGF receptor gene expression and cholinergic neuronal hypertrophy within the basal forebrain of the adult rat. Neuron. 1989 Aug;3(2):247–256. [PubMed]
  • Gage FH, Batchelor P, Chen KS, Chin D, Higgins GA, Koh S, Deputy S, Rosenberg MB, Fischer W, Bjorklund A. NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum. Neuron. 1989 Feb;2(2):1177–1184. [PubMed]
  • Martínez HJ, Dreyfus CF, Jonakait GM, Black IB. Nerve growth factor promotes cholinergic development in brain striatal cultures. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7777–7781. [PMC free article] [PubMed]
  • Mobley WC, Rutkowski JL, Tennekoon GI, Gemski J, Buchanan K, Johnston MV. Nerve growth factor increases choline acetyltransferase activity in developing basal forebrain neurons. Brain Res. 1986 Jul;387(1):53–62. [PubMed]
  • Mobley WC, Rutkowski JL, Tennekoon GI, Buchanan K, Johnston MV. Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. Science. 1985 Jul 19;229(4710):284–287. [PubMed]
  • Koliatsos VE, Shelton DL, Mobley WC, Price DL. A novel group of nerve growth factor receptor-immunoreactive neurons in the ventral horn of the lumbar spinal cord. Brain Res. 1991 Feb 8;541(1):121–128. [PubMed]
  • Armstrong DM, Brady R, Hersh LB, Hayes RC, Wiley RG. Expression of choline acetyltransferase and nerve growth factor receptor within hypoglossal motoneurons following nerve injury. J Comp Neurol. 1991 Feb 22;304(4):596–607. [PubMed]
  • Johnson EM., Jr Regulation of nerve growth factor receptor expression on Schwann cells. Prog Brain Res. 1988;78:327–331. [PubMed]
  • Taniuchi M, Schweitzer JB, Johnson EM., Jr Nerve growth factor receptor molecules in rat brain. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1950–1954. [PMC free article] [PubMed]
  • Strahler JR, Rosenbloom BB, Hanash SM. A silent, neutral substitution detected by reverse-phase high-performance liquid chromatography: hemoglobin Beirut. Science. 1983 Aug 26;221(4613):860–862. [PubMed]
  • Mufson EJ, Presley LN, Kordower JH. Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson's disease: reduced cell numbers and co-localization with cholinergic neurons. Brain Res. 1991 Jan 18;539(1):19–30. [PubMed]
  • Kordower JH, Gash DM, Bothwell M, Hersh L, Mufson EJ. Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer's patients. Neurobiol Aging. 1989 Jan-Feb;10(1):67–74. [PubMed]
  • Higgins GA, Mufson EJ. NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer's disease. Exp Neurol. 1989 Dec;106(3):222–236. [PubMed]
  • Rosene DL, Roy NJ, Davis BJ. A cryoprotection method that facilitates cutting frozen sections of whole monkey brains for histological and histochemical processing without freezing artifact. J Histochem Cytochem. 1986 Oct;34(10):1301–1315. [PubMed]
  • Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097–1105. [PubMed]
  • Emory CR, Ala TA, Frey WH., 2nd Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles. Neurology. 1987 May;37(5):768–772. [PubMed]
  • Al-Ghoul WM, Miller MW. Transient expression of Alz-50 immunoreactivity in developing rat neocortex: a marker for naturally occurring neuronal death? Brain Res. 1989 Mar 6;481(2):361–367. [PubMed]
  • Hamre KM, Hyman BT, Goodlett CR, West JR, Van Hoesen GW. Alz-50 immunoreactivity in the neonatal rat: changes in development and co-distribution with MAP-2 immunoreactivity. Neurosci Lett. 1989 Apr 10;98(3):264–271. [PubMed]
  • Ferreira A, Busciglio J, Cáceres A. An immunocytochemical analysis of the ontogeny of the microtubule-associated proteins MAP-2 and Tau in the nervous system of the rat. Brain Res. 1987 Jul;431(1):9–31. [PubMed]
  • Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451. [PubMed]
  • Hohn A, Leibrock J, Bailey K, Barde YA. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990 Mar 22;344(6264):339–341. [PubMed]
  • Johnson D, Lanahan A, Buck CR, Sehgal A, Morgan C, Mercer E, Bothwell M, Chao M. Expression and structure of the human NGF receptor. Cell. 1986 Nov 21;47(4):545–554. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...