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PMID: 14660786 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Increased hippocampal neurogenesis in Alzheimer's disease.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 1 ·2004-01-06 ·Pages 343-7

Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA

Abstract

Neurogenesis, which persists in the adult mammalian brain, may provide a basis for neuronal replacement therapy in neurodegenerative diseases like Alzheimer's disease (AD). Neurogenesis is increased in certain acute neurological disorders, such as ischemia and epilepsy, but the effect of more chronic neurodegenerations is uncertain, and some animal models of AD show impaired neurogenesis. To determine how neurogenesis is affected in the brains of patients with AD, we investigated the expression of immature neuronal marker proteins that signal the birth of new neurons in the hippocampus of AD patients. Compared to controls, Alzheimer's brains showed increased expression of doublecortin, polysialylated nerve cell adhesion molecule, neurogenic differentiation factor and TUC-4. Expression of doublecortin and TUC-4 was associated with neurons in the neuroproliferative (subgranular) zone of the dentate gyrus, the physiological destination of these neurons (granule cell layer), and the CA1 region of Ammon's horn, which is the principal site of hippocampal pathology in AD. These findings suggest that neurogenesis is increased in AD hippocampus, where it may give rise to cells that replace neurons lost in the disease, and that stimulating hippocampal neurogenesis might provide a new treatment strategy.

MeSH Terms
Adolescent Adult Aged Aged, 80 and over Alzheimer Disease/metabolism,pathology Animals Basic Helix-Loop-Helix Transcription Factors Case-Control Studies Doublecortin Domain Proteins Female Hippocampus/metabolism,pathology Humans Immunohistochemistry Male Microtubule-Associated Proteins Middle Aged Nerve Degeneration/metabolism,pathology Nerve Tissue Proteins/metabolism Neural Cell Adhesion Molecule L1/metabolism Neurons/metabolism,pathology Neuropeptides/metabolism Sialic Acids/metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors Doublecortin Domain Proteins Microtubule-Associated Proteins Nerve Tissue Proteins Neural Cell Adhesion Molecule L1 Neuropeptides Sialic Acids polysialyl neural cell adhesion molecule Neurogenic differentiation factor 1
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Jin Kunlin
Buck Institute for Age Research, Novato, CA 94945, USA.
Peel Alyson L
Mao Xiao Ou
Xie Lin
Cottrell Barbara A
Henshall David C
Greenberg David A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.2634794100
Published
2004-01-06
Epub
2003-00-05
Pages
343-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC314187
Subset
IM
Grants
NINDS NIH HHS · R01 NS044921 · United States
NIMH NIH HHS · MH/NS31862 · United States
External Links
PubMed source DOI: 10.1073/pnas.2634794100 PMC Full Text View journal details
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