Increased Hippocampal Neurogenesis in Alzheimer's Disease
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 c...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 1; pp. 343 - 347 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
06.01.2004
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 To whom correspondence should be addressed at: Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945. E-mail: dgreenberg@buckinstitute.org. This paper was submitted directly (Track II) to the PNAS office. Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD Abbreviations: Aβ, β-amyloid peptide; AD, Alzheimer's disease; APP, amyloid precursor protein; DCX, doublecortin; DG, dentate gyrus; GCL, granule cell layer; NeuN, neuronal nuclear antigen; NeuroD, neurogenic differentiation factor; NFTs, neurofibrillary tangles; PSA-NCAM, polysialylated neural cell adhesion molecule; SGZ, subgranular zone. K.J. and A.L.P. contributed equally to this work. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2634794100 |