Fibrinogen’s potential role in connecting cerebrovascular abnormalities with glymphatic dysfunction in Alzheimer’s disease

Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated tau.However,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological mechanism.An often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and microhemorrhages.Animal models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).