Plasma Aβ: A Possible Missing Link Between Alzheimer Disease and Diabetes

  1. Ryuichi Morishita1
  1. 1Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan
  2. 2Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
  1. Corresponding authors: Naoyuki Sato, nsato{at}cgt.med.osaka-u.ac.jp, and Ryuichi Morishita, morishit{at}cgt.med.osaka-u.ac.jp.

Currently, there are more than 30 million dementia patients worldwide (1). More than half of dementia is caused by Alzheimer disease (AD), which consists of both familial and sporadic forms. Familial AD is caused by mutations in the amyloid precursor protein (APP) (2) and presenilin genes (3). Both mutations cause overproduction of amyloid-β (Aβ), particularly its longer form, Aβ42, which is more prone to aggregate. It should be noted that familial AD accounts for a small proportion of all AD cases. On the other hand, sporadic cases comprise more than 95% of AD, and emerging evidence suggests that diabetes is a nongenetic risk factor for sporadic AD (4). While diabetes increases AD 1.5–2-fold, the mechanism whereby diabetes enhances AD risk has not been elucidated. As 285 million people battle diabetes worldwide against the backdrop of an aging society (5), understanding the relationship between AD and diabetes is of extreme importance.

Interestingly, several clinical reports have suggested that AD patients also have glucose intolerance, suggesting a bidirectional relationship between the two conditions (6,7). Supporting this idea are data from animal models such as APP + ob/ob mice showing that AD aggravates the diabetic phenotype (8,9). Although further evidence is still required to confirm this concept, it is intriguing to investigate the …

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