Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry

• DOI: 10.1186/s40478-017-0477-x
• Publication Date: 2017-10-16T07:57:19Z
• Authors: Nobuto Kakuda; Tomohiro Miyasaka; Noriyuki Iwasaki; Takashi Nirasawa; Satoko Wada-Kakuda; Junko Takahashi-F...; Shigeo Murayama; Yasuo Ihara; Masaya Ikegawa
• Keywords: Mass spectrometry imaging; Amyloid (mycology)

Amyloid β (Aβ) deposition in the brain is an early and invariable feature of Alzheimer's disease (AD). The Aβ peptides are composed about 40 amino acids generated from amyloid precursor proteins (APP), by β- γ-secretases. distribution individual brains aged people, those suffering AD cerebral angiopathy (CAA), not fully characterized. We employed matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) to illustrate spatial a broad range species human autopsied brains. With technical advancements such as formic acid pretreatment frozen samples, we have: i) demonstrated that Aβ1–42 Aβ1–43 were selectively deposited senile plaques while full-length Aβ1–36, 1–37, 1–38, 1–39, 1–40, Aβ1–41 leptomeningeal blood vessels. ii) Visualized distinct depositions N-terminal truncated Aβ40 Aβ42, including pyroglutamate modified at Glu-3 (N3pE), only with IMS for first time. iii) Demonstrated one single alteration C-terminus between results profound changes their pattern. In vitro, this can be attributed difference self-aggregation ability amongst Aβ1–40, Aβ1–41, Aβ1–42. These observations further confirmed immunohistochemistry (IHC), using newly developed anti-Aβ1–41 antibody. Here, and/or C- fragments Aβs CAA MALDI-IMS visualized spacio-temporal specific manner. Specifically, was detected both IHC suggesting drastic changes. suggest could used standard approach combination clinical, genetic, pathological understanding pathology CAA.