Astroglial atrophy in Alzheimer’s disease

Abstract

Astrocytes, a class of morphologically and functionally diverse primary homeostatic neuroglia, are key keepers of neural tissue homeostasis and fundamental contributors to brain defence in pathological contexts. Failure of astroglial support and defence facilitate the evolution of neurological diseases, which often results in aberrant synaptic transmission, neurodegeneration, and death of neurones. disease (AD) astrocytes undergo complex and multifaceted metamorphoses ranging from atrophy with loss of function to reactive astrogliosis with hypertrophy. Astroglial asthenia underlies reduced homeostatic support and neuroprotection that may account for impaired synaptic transmission and neuronal demise. Reactive astrogliosis which mainly develops in astrocytes associated with senile plaque is prominent at the early to moderate stages of AD manifested by mild cognitive impairment; down-regulation of astrogliosis (reflecting astroglial paralysis) is associated with late stages of the disease characterised by severe dementia. Cellspecific therapies aimed at boosting astroglial supportive and defensive capabilities and preventing astroglial paralysis may offer new directions in preventing, arresting or even curing AD-linked neurodegeneration.

Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation

“…Our findings of pronounced morphological atrophy in human iPSCs parallel recent demonstration of similar morphological atrophy in iPSC-derived astrocytes generated from early familial and late sporadic AD patients [45]. Morphological atrophy of astrocytes is arguably associated with neuronal damage (due to failed homeostatic support) and aberrant synaptic connectivity manifest in neurodegenerative and psychiatric diseases (for a review see [42]). In many cases, astrocytic atrophy precedes cell death and neuronal degeneration.…”

“…Subsequent studies revealed that functional exhaustion and loss of astroglial homeostatic support are dominant glial contribution to the PD, and the special definition of "dysfunctional" astrocytes has been introduced [38,39]. Astroglial asthenia, atrophy and loss of homeostatic and neuroprotective capacities were noted in aging [40] and in various neurodegenerative and neuropsychiatric diseases [41,42]; astroglial atrophy thus represents a defined class of astrogliopathies [43].…”

Caloric restriction triggers morphofunctional remodeling of astrocytes and enhances synaptic plasticity in the mouse hippocampus

“…therapeutic action remains unclear. At the early stages, both Alzheimer's disease and epilepsy are associated with astrocyte atrophy 29,74 . The growth of astrocytic processes induced by CR counteracts this pathological remodeling.…”

Astrocytes dystrophy in ageing brain parallels impaired synaptic plasticity

“…These conceptualisations, however, are based on relatively thin data when it comes to astrogliosis; the ubiquitous gliosis is further questioned by well documented presence of dystrophic microglia in the aged human brains (Conde and Streit, 2006). There are substantial arguments for a decrease in functional capacities of neuroglial cells in ageing, with glial dystrophy and paralysis facilitating neurodegeneration (Streit et al, 2020;Verkhratsky et al, 2015;Verkhratsky et al, 2019).…”