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Reconsidering Alzheimer’s Pathology and Hippocampal Neurogenesis.

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Most investigations using transgenic animal models of Alzheimer’s disease (AD) have reported a decrease in hippocampal neurogenesis (Demars et al., 2010, Hamilton et al., 2010, Naumann et al., 2010). Currently, is considered that the impairment in neurogenesis can be an important factor during the onset and progression of AD. Most authors consider hippocampal neurogenesis necessary to maintain hippocampal cognitive abilities, therefore, the damage in the proliferative system has to be functionally detrimental (See references in Mu and Gage, 2011). Most animal models with the familial type mutations that cause AD show that when toxic amyloid beta peptides (Aβ42) are present, hippocampal neurogenesis decreases. In addition, we know that knocking out of presenilin-1 in the hippocampus impairs proliferation. The general agreement is that all mutations related with AD should be damaging for adult neurogenesis with the consequent cognitive impairment. Considering this, it is notorious that ,for the surprise of the authors, Yetman and Jankowsky (2013) showed no impact on neurogenesis caused by a strong Human amyloid precursor protein (hAPP) overexpression. This happens when hAPP expression excludes the proliferative area of the dentate gyrus.
In front of a large amount of data obtained from animal models, how neurogenesis responds to AD in humans remains understudied. Still, the available evidence show either no alteration on neurogenesis during AD or a significant increase on proliferation and survival of new neurons (Jin et al., 2004, Perry et al., 2012). In 2004, Jin and colleagues showed that AD increases neurogenesis markers, not only during the onset, but also during the middle and advanced stages of the disease, results confirme...

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Mu Y, Gage FH (2011) Adult hippocampal neurogenesis and its role in Alzheimer's disease. Molecular neurodegeneration 6:85.
Naumann N, Alpar A, Ueberham U, Arendt T, Gartner U (2010) Transgenic expression of human wild-type amyloid precursor protein decreases neurogenesis in the adult hippocampus. Hippocampus 20:971-979.
Perry EK, Johnson M, Ekonomou A, Perry RH, Ballard C, Attems J (2012) Neurogenic abnormalities in Alzheimer's disease differ between stages of neurogenesis and are partly related to cholinergic pathology. Neurobiol Dis 47:155-162.
West MJ, Coleman PD, Flood DG, Troncoso JC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet 344:769-772.
Yetman MJ, Jankowsky JL (2013) Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment. J Neurosci 33:17335-17341.
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