Alzheimer's & dementia : the journal of the Alzheimer's Association
-
The mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following amyloid β (Aβ) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer's pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. ⋯ People with DS and trisomy 21 produce a large amount of Aβ. If Alzheimer's pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Aβ mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer's disease changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.