Title:Platelets in Alzheimer’s Disease-Associated Cellular Senescence and Inflammation
Volume: 19
Issue: 9
Author(s): Tiziana Casoli, Marta Balietti, Belinda Giorgetti, Moreno Solazzi, Osvaldo Scarpino and Patrizia Fattoretti
Affiliation:
Keywords:
Alzheimer’s disease, platelets, inflammation, senescence, amyloid, therapeutic targets, aging, glia, neurons, aspirin
Abstract: Alzheimer’s disease (AD) is a complex degenerative disorder of the brain, associated with a progressive cognitive decline.
Age is the main risk factor with almost half of the population above 90 years affected by this pathology. AD and brain aging share common
molecular changes, so it has been hypothesized that AD could be a form of accelerated brain aging. In this context, senescenceassociated
mechanisms could be a valuable target of investigation both to analyze the causes of this disease and to define therapeutic
strategies. Senescent phenotypes of glia and neurons, as well as of peripheral cells, have been described in AD. Much evidence indicate
that vascular impairment is a fundamental contributor to AD pathology and platelets are generally considered a key element because they
represent the link between amyloid-ß (Aß) deposition, peripheral inflammation and endothelial senescence. Both activated and senescent
platelets are a source of Aß, in addition activated platelets secrete many proinflammatory mediators that could contribute to increased peripheral
inflammation and endothelial senescence. Treatments aimed to target peripheral endothelial senescence include antioxidants and
some substances, such as aspirin, that modulate platelet aggregation and inflammatory response. Heparin has been proposed as a treatment
for senile dementia and exhibits anti-inflammatory action as well as inhibitory effects on Aß assembly. Identifying peripheral targets
for AD treatments could also result advantageous as it would be possible to monitor directly their efficacy. Nevertheless more research
is needed to clarify all the different aspects and interactions of blood cells, vascular cells and their secretory products.
