Affiliations: Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, USA
Correspondence:
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Correspondence to: Miguel A. Lopez-Toledano, Department of Neuroscience, The Scripps Research Institute, 130 Scripps Way #3C2, Jupiter, FL, USA. Tel.: +1 561 228 3516; Fax: +1 561 228 3079; E-mail: malopez@scripps.edu.
Abstract: Alzheimer's disease (AD) is a devastating age-related neurodegenerative disorder characterized by progressive impairment of cognition and short-term memory loss. The deposition of amyloid-β (Aβ) 1-42 into senile plaques is an established feature of AD neuropathology. Controversy still exists about the amyloid pathway as the initiating mechanism or a mere consequence of the events leading to AD. Nevertheless, Aβ toxicity has been probed in vitro and in vivo and increased production or decreased clearance of Aβ peptides are reported to play a major role in the development of AD. Treatment of neural stem cells with Aβ in vitro induces neuronal differentiation. Increased neurogenesis has been also described in AD patients as well as in amyloid-β protein precursor (AβPP) transgenic mice. Adult neurogenesis is greatly enhanced in young AβPP transgenic mice, before other AD-liked pathologies, and reduced in older animals. This increased neurogenesis at young ages might be the first pathology related to AD, which is detectable long before other harmful manifestation of the disease. Therefore, understanding the mechanisms of Aβ-induced neurogenesis will reveal insights into the pathogenesis of AD and may prove useful as an early AD biomarker.
