“…Emerging evidence demonstrates that common genetic, as well as reversible or nonreversible, risk factors directly contribute to the cognitive deficits and demyelination seen in mild cognitive impairment, AD and dementias, and normative aging. 50 From this perspective, the breakdown of myelin may promote the deposition of amyloid-beta fibrils, which in turn causes further myelin breakdown and neurodegeneration. 6 Indeed, a central role for myelination disorders in AD and dementia, as a complement to the amyloid hypothesis, has been put forward to account for the limited outcomes of clinical trials targeting amyloid, and shifts the focus of AD pathology from the burden of discrete lesions to include an emphasis on brain circuitry disruption, including in WM due to axonal degeneration or myelin breakdown.…”