Neuroanatomy & Pathology of sporadic Alzheimer’s disease

This text is the brainchild of Heiko Braak and his wife Kelly de Tredici and represents the most sophisticated synthesis of their version of the cascade of pathology in Alzheimer’s. Starting with long, unmyelinated fibres which stretch from brain stem to frontal cortex, tau Pathology begins to build up in the middle of life, and gradually spreads through adjoining areas until the hippocampus is affected and the first cortical signs – classically memory deficits – appear. In Braak’s vision, tau-opathy leads to downstream amyloid accumulation and cellular death, but this is after decades of accumulated cellular decline and dysfunction because of the pure energy expense of powering unmyelinated cells with heavily ramified axons – and their resulting vulnerability to oxidative stress.

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