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      Adult Hippocampal Neurogenesis in Aging and Alzheimer's Disease

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          Abstract

          Cognitive deficits associated with Alzheimer's disease (AD) severely impact daily life for the millions of affected individuals. Progressive memory impairment in AD patients is associated with degeneration of the hippocampus. The dentate gyrus of the hippocampus, a region critical for learning and memory functions, is a site of adult neurogenesis in mammals. Recent evidence in humans indicates that hippocampal neurogenesis likely persists throughout life, but declines with age and is strikingly impaired in AD. Our understanding of how neurogenesis supports learning and memory in healthy adults is only beginning to emerge. The extent to which decreased neurogenesis contributes to cognitive decline in aging and AD remains poorly understood. However, studies in rodent models of AD and other neurodegenerative diseases raise the possibility that targeting neurogenesis may ameliorate cognitive dysfunction in AD. Here, we review recent progress in understanding how adult neurogenesis is impacted in the context of aging and AD.

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          Most cited references121

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          Neuropathological stageing of Alzheimer-related changes

          Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.
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            The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics.

            It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid beta-peptide (Abeta) in plaques in brain tissue. According to the amyloid hypothesis, accumulation of Abeta in the brain is the primary influence driving AD pathogenesis. The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Abeta production and Abeta clearance.
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              Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

              The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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                Author and article information

                Contributors
                Journal
                Stem Cell Reports
                Stem Cell Reports
                Stem Cell Reports
                Elsevier
                2213-6711
                25 February 2021
                13 April 2021
                25 February 2021
                : 16
                : 4
                : 681-693
                Affiliations
                [1 ]Graduate Program in Neuroscience, Brown University, Providence, RI 02912, USA
                [2 ]Warren Alpert Medical School of Brown University, Providence, RI 02912, USA
                [3 ]Department of Neuroscience, Brown University, Providence, RI 02912, USA
                [4 ]Carney Institute for Brain Science, Brown University, Providence, RI 02912, USA
                [5 ]Center for Translational Neuroscience, Brown University, Providence, RI 02912, USA
                [6 ]Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
                [7 ]Center on the Biology of Aging, Brown University, Providence, RI 02912, USA
                Author notes
                []Corresponding author ashley_webb@ 123456brown.edu
                Article
                S2213-6711(21)00049-7
                10.1016/j.stemcr.2021.01.019
                8072031
                33636114
                e93df41e-15d2-41ce-8a60-0db11c499982
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                adult neurogenesis,aging,alzheimer's disease,cognitive decline,neural stem cell

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