Does the difference between PART and Alzheimer’s disease lie in the age-related changes in cerebral arteries that trigger the accumulation of Aβ and propagation of tau?

Weller, Roy O.; Hawkes, Cheryl A.; Carare, Roxana O. and Hardy, John (2015). Does the difference between PART and Alzheimer’s disease lie in the age-related changes in cerebral arteries that trigger the accumulation of Aβ and propagation of tau? Acta Neuropathologica, 129(5) pp. 763–766.

DOI: https://doi.org/10.1007/s00401-015-1416-1

Abstract

Primary age-related tauopathy (PART) is characterised by a limited distribution of tau pathology, compared with Alzheimer’s disease (AD), and an absence of amyloid-β (Aβ) plaques. Clinically, patients with PART are older and only a minority have profound cognitive impairment. Neurofibrillary tangles (NFTs) containing hyperphosphorylated tau spread in an age-related manner from brainstem to cerebral cortical areas and the presence of Aβ plaques is associated with acceleration in the propagation of NFTs in the pathogenesis of AD. The amyloid cascade appears to drive the hyperphosphorylation and propagation of tau and Aβ oligomers have a toxic effect upon synapses.

In the context of PART, we ask the question “Why is there relatively limited spread of NFTs and few if any Aβ plaques in PART compared with AD?” In order to answer these questions, we examine evidence that ageing of cerebral arteries is a trigger for the amyloid cascade and propagation of tau and NFTs. We propose that age-related changes in cerebral arteries impair the perivascular elimination of Aβ and other metabolites from the brain leading to a loss of homoeostasis within the brain, to seeding of plaques of insoluble Aβ and to acceleration of the propagation of tau/NFTs pathology

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