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PMID: 19699201 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Neurogenesis and Alzheimer's disease: at the crossroads.

Experimental neurology ·Vol. 223 ·No. 2 ·2010-06-00 ·Pages 267-81

Lazarov O, Marr RA

Abstract

While a massive and progressive neuronal loss in specific areas such as the hippocampus and cortex unequivocally underlies cognitive deterioration and memory loss in Alzheimer's disease, noteworthy alterations take place in the neurogenic microenvironments, namely, the subgranule layer of the dentate gyrus and the subventricular zone. Compromised neurogenesis presumably takes place earlier than onset of hallmark lesions or neuronal loss, and may play a role in the initiation and progression of neuropathology in Alzheimer's disease. Neurogenesis in the adult brain is thought to play a role in numerous forms and aspects of learning and memory and contribute to the plasticity of the hippocampus and olfactory system. Misregulated or impaired neurogenesis on the other hand, may compromise plasticity and neuronal function in these areas and exacerbate neuronal vulnerability. Interestingly, increasing evidence suggests that molecular players in Alzheimer's disease, including PS1, APP and its metabolites, play a role in adult neurogenesis. In addition, recent studies suggest that alterations in tau phosphorylation are pronounced in neurogenic areas, and may interfere with the potential central role of tau proteins in neuronal maturation and differentiation. On the other hand, numerous neurogenic players, such as Notch-1, ErbB4 and L1 are substrates of alpha- beta- and gamma- secretase that play a major role in Alzheimer's disease. This review will discuss current knowledge concerning alterations of neurogenesis in Alzheimer's disease with specific emphasis on the cross-talk between signaling molecules involved in both processes, and the ways by which familial Alzheimer's disease-linked dysfunction of these signaling molecules affect neurogenesis in the adult brain.

MeSH Terms
Alzheimer Disease/pathology,physiopathology Brain/pathology,physiopathology Humans Neurogenesis/physiology
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lazarov Orly
Department of Anatomy and Cell Biology, College of Medicine, 808 S Wood St. M/C 512, University of Illinois at Chicago, Chicago, IL 60612, USA. [email protected]
Marr Robert A
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Article Info
Journal
Experimental neurology
Abbr.
Exp Neurol
ISSN
1090-2430
DOI
10.1016/j.expneurol.2009.08.009
Email
[email protected]
Published
2010-06-00
Epub
2009-00-19
Pages
267-81
Language
English
Region
United States
NLM ID
0370712
PMCID
PMC2864344
Subset
IM
Grants
NIA NIH HHS · R01 AG033570 · United States
NIA NIH HHS · R01 AG033570-01 · United States
External Links
PubMed source DOI: 10.1016/j.expneurol.2009.08.009 PMC Full Text View journal details
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