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A beta(38) in the Brains of Patients with Sporadic and Familial Alzheimer's Disease and Transgenic Mouse Models
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2014 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 39, no 4, 871-881 p.Article in journal (Refereed) Published
Abstract [en]

The pathogenesis of Alzheimer's disease (AD) is believed to be closely dependent on deposits of neurotoxic amyloid-beta peptides (A beta), which become abundantly present throughout the central nervous system in advanced stages of the disease. The different A beta peptides existing are generated by subsequent cleavage of the amyloid-beta protein precursor (A beta PP) and may vary in length and differ at their C-terminus. Despite extensive studies on the most prevalent species A beta(40) and A beta(42), A beta peptides with other C-termini such as A beta(38) have not received much attention. In the present study, we used a highly specific and sensitive antibody against A beta(38) to analyze the distribution of this A beta species in cases of sporadic and familial AD, as well as in the brains of a series of established transgenic AD mouse models. We found A beta(38) to be present as vascular deposits in the brains of the majority of sporadic AD cases, whereas it is largely absent in non-demented control cases. A beta(38)-positive extracellular plaques were virtually limited to familial cases. Interestingly we observed A beta(38)-positive plaques not only among familial cases due to A beta PP mutations, but also in cases of familial AD caused by presenilin (PSEN) mutations. Furthermore we demonstrate that A beta(38) deposits in the form of extracellular plaques are common in several AD transgenic mouse models carrying either only A beta PP, or combinations of A beta PP, PSEN1, and tau transgenes.

Place, publisher, year, edition, pages
2014. Vol. 39, no 4, 871-881 p.
Keyword [en]
A beta(38), A beta PP, amyloid, mutations, presenilin, transgenic mice, vasculature, vessels
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-221732DOI: 10.3233/JAD-131373ISI: 000331842500017OAI: oai:DiVA.org:uu-221732DiVA: diva2:710144
Available from: 2014-04-04 Created: 2014-04-03 Last updated: 2014-04-04Bibliographically approved

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Lannfelt, LarsIngelsson, Martin
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