Integrated phylogeny of the human brain and pathobiology of Alzheimer’s disease: A unifying hypothesis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F21%3A43920567" target="_blank" >RIV/00023752:_____/21:43920567 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/21:43921387

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0304394021002731?via%3Dihub#" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0304394021002731?via%3Dihub#</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.neulet.2021.135895" target="_blank" >10.1016/j.neulet.2021.135895</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Integrated phylogeny of the human brain and pathobiology of Alzheimer’s disease: A unifying hypothesis

Popis výsledku v původním jazyce

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 increase in life expectancy overwhelm the fine homeostatic balance and trigger the disease process.

Název v anglickém jazyce

Integrated phylogeny of the human brain and pathobiology of Alzheimer’s disease: A unifying hypothesis

Popis výsledku anglicky

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 increase in life expectancy overwhelm the fine homeostatic balance and trigger the disease process.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/LO1611" target="_blank" >LO1611: Udržitelnost pro Národní ústav duševního zdraví</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neuroscience Letters

ISSN

0304-3940

e-ISSN

—

Svazek periodika

755

Číslo periodika v rámci svazku

135895

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

1-9

Kód UT WoS článku

000644937300004

EID výsledku v databázi Scopus

2-s2.0-85105834527