TY - JOUR
T1 - Aβ∗56 is a stable oligomer that impairs memory function in mice
AU - Liu, Peng
AU - Lapcinski, Ian P.
AU - Hlynialuk, Chris J.W.
AU - Steuer, Elizabeth L.
AU - Loude, Thomas J.
AU - Shapiro, Samantha L.
AU - Kemper, Lisa J.
AU - Ashe, Karen H.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/3/15
Y1 - 2024/3/15
N2 - Amyloid-β (Aβ) oligomers consist of fibrillar and non-fibrillar soluble assemblies of the Aβ peptide. Aβ∗56 is a non-fibrillar Aβ assembly that is linked to memory deficits. Previous studies did not decipher specific forms of Aβ present in Aβ∗56. Here, we confirmed the memory-impairing characteristics of Aβ∗56 and extended its biochemical characterization. We used anti-Aβ(1-x), anti-Aβ(x-40), anti-Aβ(x-42), and A11 anti-oligomer antibodies in conjunction with western blotting, immunoaffinity purification, and size-exclusion chromatography to probe aqueous brain extracts from Tg2576, 5xFAD, and APP/TTA mice. In Tg2576, Aβ∗56 is a ∼56-kDa, SDS-stable, A11-reactive, non-plaque-dependent, water-soluble, brain-derived oligomer containing canonical Aβ(1-40). In 5xFAD, Aβ∗56 is composed of Aβ(1-42), whereas in APP/TTA, it contains both Aβ(1-40) and Aβ(1-42). When injected into the hippocampus of wild-type mice, Aβ∗56 derived from Tg2576 mice impairs memory. The unusual stability of this oligomer renders it an attractive candidate for studying relationships between molecular structure and effects on brain function.
AB - Amyloid-β (Aβ) oligomers consist of fibrillar and non-fibrillar soluble assemblies of the Aβ peptide. Aβ∗56 is a non-fibrillar Aβ assembly that is linked to memory deficits. Previous studies did not decipher specific forms of Aβ present in Aβ∗56. Here, we confirmed the memory-impairing characteristics of Aβ∗56 and extended its biochemical characterization. We used anti-Aβ(1-x), anti-Aβ(x-40), anti-Aβ(x-42), and A11 anti-oligomer antibodies in conjunction with western blotting, immunoaffinity purification, and size-exclusion chromatography to probe aqueous brain extracts from Tg2576, 5xFAD, and APP/TTA mice. In Tg2576, Aβ∗56 is a ∼56-kDa, SDS-stable, A11-reactive, non-plaque-dependent, water-soluble, brain-derived oligomer containing canonical Aβ(1-40). In 5xFAD, Aβ∗56 is composed of Aβ(1-42), whereas in APP/TTA, it contains both Aβ(1-40) and Aβ(1-42). When injected into the hippocampus of wild-type mice, Aβ∗56 derived from Tg2576 mice impairs memory. The unusual stability of this oligomer renders it an attractive candidate for studying relationships between molecular structure and effects on brain function.
KW - Biochemistry
KW - Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85185769103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85185769103&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.109239
DO - 10.1016/j.isci.2024.109239
M3 - Article
C2 - 38433923
AN - SCOPUS:85185769103
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 3
M1 - 109239
ER -