Ovsepian, Saak, O'Leary, Valerie, Hoschl, Cyril and Zaborszky, Laszlo (2021) Integrated phylogeny of the human brain and pathobiology of Alzheimer's disease: a unifying hypothesis. Neuroscience Letters, 11 (755):135895. pp. 1-9. ISSN 0304-3940 (Print), 0304-3940 (Online) (doi:10.1016/j.neulet.2021.135895)

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Abstract

The disproportionate evolutionary expansion of the human cerebral cortex with reinforcement of cholinergic innervations warranted a major rise in the functional and metabolic load of the conserved basal forebrain (BF) cholinergic system. Given that acetylcholine (ACh) regulates properties of the microtubule-associated protein (MAP) tau and promotes non-amyloidogenic processing of amyloid precursor protein (APP), growing neocortex predicts higher demands for ACh, while the emerging role of BF cholinergic projections in Aβ clearance infers greater exposure of source neurons and their innervation fields to amyloid pathology. The higher exposure of evolutionary most recent cortical areas to the amyloid pathology of Alzheimer's disease (AD) with synaptic impairments and atrophy, therefore, might involve attenuated homeostatic effects of BF cholinergic projections, in addition to fall-outs of inherent processes of expanding association areas. This unifying model, thus, views amyloid pathology and loss of cholinergic cells as a quid pro quo of the allometric evolution of the human brain, which in combination with an increase in life expectancy overwhelm the fine homeostatic balance and trigger the disease process.

Item Type:	Article
Uncontrolled Keywords:	brain evolution; cholinergic neurons; p75 NTR; amyloid deposition; cortical expansion; default mode networks; Alzheimer’s disease
Subjects:	R Medicine > RB Pathology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > Biology & Biotechnology Research Group Faculty of Engineering & Science > School of Science (SCI)
Related URLs:	Publisher
Last Modified:	12 Jun 2022 01:38
URI:	http://gala.gre.ac.uk/id/eprint/35158

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