Role of BRI2 in dementia.
Alzheimer's disease (AD), the most common form of dementia, shares clinical and pathological similarities with familial British and Danish dementias (FBD and FDD). Whereas the etiology of sporadic AD remains unclear, familial AD is linked to mutations in amyloid-β protein precursor (AβPP), presenilin 1 (PS1), and presenilin 2 (PS2). Similarly, FBD and FDD originate from mutations in the BRI2 gene (or ITM2b), causing amyloid angiopathy and neurofibrillary tangles analogous to those observed in AD. Recent studies on the role of BRI2 in FBD and FDD have revealed that the three diseases may share pathophysiological pathways leading to dementia. Interestingly, BRI2 is a potential regulator of AβPP processing, and it can inhibit the production and fibrillation of Aβ. This suggests a role of BRI2 in the amyloid cascade, which is the prevailing hypothesis about AD pathogenesis. To understand a possible relationship of BRI2 with AD, we reviewed the relevant studies on this protein. The data included not only the protein's structure, expression pattern, function, and involvement in FBD and FDD, but also its relationship with memory deficits and the main pathological proteins involved in AD. Thus, we highlight and discuss the potential links between BRI2 and AD, leading to the formulation of a modified hypothesis about AD etiology.
Neurochemistry Laboratory Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Marta
M
Del Campo
Neurochemistry Laboratory Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
Charlotte E
CE
Teunissen
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000378:metabolism; D003704:Dementia / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C120083:ITM2B protein, human; D008562:Membrane Glycoproteins
Alzheimer's disease; amyloid-β; amyloid-β protein precursor; familial British dementia (FBD); familial Danish dementia (FDD); integral membrane protein 2B (ITM2B/BRI2)