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Ischemic axonopathy: The missing link between cardiocerebral hypotension, white matter loss, and Alzheimer's disease
Author(s) -
Ball Melvyn J.
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.06.003
Subject(s) - neurology , white paper , citation , white matter , disease , psychology , medicine , gerontology , psychiatry , library science , computer science , political science , law , magnetic resonance imaging , radiology
To the Editor, Some years ago, I published two brief reports [1,2] positing that a phenomenon that might be called “ischemic axonopathy” was the best explanation for the rarefaction of white matter seen frequently in Alzheimer’s disease (AD). Of late, there has been considerable new momentum to claim AD is primarily, or at least initially, a disease of myelin in white matter [3]. Careful histopathological examinations surely establish that this is incorrect. There is, for example, no evidence for substantial oligodendroglial myelin breakdown products in macrophages in such white matter. More particularly, the apparent decreased health of the diminished, hypodensewhite matter is certainly not the result of amyloid beta deposition “blocking” the flow of cerebrospinal fluid (CSF) in widened perivascular spaces, despite the claim made byRoher et al. [4]. In their zeal to gather and analyze biochemically the leptomeningeal arteries, they have never examined systematically and histologically these small but critical vessels in sufficient numbers of such cases. If they had, they would have frequently seen a unique “double-lumen” appearance, described decades ago by Romanul and Abramowitz [5], which reflects transient episodes of systemic hypotension (very common in the elderly and especially in those with cardiac troubles), during which the flow through thesemeningeal arteries is temporarilydecreased. (Abreached blood–brain barrier releasing fibrinogen, plus damaged endothelial cell production of thrombin, maywell interact to evoke altered thrombosis, generating lysis-resistant clots.) When the systemic and associated intra-arterial cerebral pressures return to normal, these vessels have reendothelialized the transient thromboses of their lumina to form a new, smaller internal diameter—hence their characteristic pathognomonic double-lumina histopathology. General autopsy findings on the elderly very often include multiple, small areas of myocardial fibrosis throughout heart muscle, despite no documented history of major heart attack. Pathologists deem these findings clear evidence of silent infarcts of the heart muscle. It