Characterization of monomeric and soluble aggregated A? in Down’s syndrome and Alzheimer’s disease brains

The major characteristics of Alzheimer’s disease (AD) are amyloid plaques, consisting aggregated beta (A?) peptides, together with tau pathology (tangles, neuropil treads and dystrophic neurites surrounding the plaques), in brain. Down’s syndrome (DS) individuals at increased risk to develop AD-type pathology; most DS have developed substantial already age 40. an extra copy chromosome 21, harbouring precursor protein gene (APP). Our aim was investigate A? peptide pattern AD brains differences their deposition aggregation, respectively. Cortical tissue from patients (with pathology), sporadic controls were homogenized fractionated into TBS (water soluble) formic acid insoluble) fractions. Immunoprecipitation (IP) performed using a variety antibodies targeting different species including oligomeric A?. Mass spectrometry then used evaluate presence patient groups. A large number peptides identified A?1-X, 2-X, 3-X, 4-X, 5-X, 11-X, extended N terminally BACE1 cleavage site ending amino 15 sequence APP/A?(-X 15), as well post-translationally modified by pyroglutamate formation. Most had higher abundance compared controls, except 15) which abundant followed AD. Furthermore, abundancies A?X-40 A?X-34 A?1-40, A?1-42, A?4-42 main constitutes protofibrils (IP’d mAb158) relative A?1-42 signals obtained samples IP’d 6E10 + 4G8, indicating that protofibrils/oligomers enriched 42. All found also present similar pathways production, degradation accumulation, for 15). Likewise, forming both similar, implying possibility treatment clinical benefit might be beneficial subjects DS.