TITLE:
Alzheimer’s Disease Aβ-Amyloid Plaque Morphology Varies According to APOE Isotype
AUTHORS:
Ina Caesar, K. Peter R. Nilsson, Per Hammarström, Mikael Lindgren, Stefan Prokop, James Schmeidler, Vahram Haroutunian, David M. Holtzman, Patrick R. Hof, Sam Gandy
KEYWORDS:
Alzheimer’s Disease, Amyloid, Apolipoprotein, Luminescent Conjugated Oligothiophenes, Hyperspectral Separation
JOURNAL NAME:
World Journal of Neuroscience,
Vol.13 No.3,
August
4,
2023
ABSTRACT: Background: The
apolipoprotein E (APOE, gene; apoE,
protein) ε4 allele is the most commonly
identified genetic risk factor for typical late-onset sporadic Alzheimer’s
disease (AD). Each APOE ε4 allele roughly triples the relative
risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence
imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to
elucidate protein aggregate structure and morphology in fresh frozen prefrontal
cortex samples from human postmortem AD brain tissue samples from patients
homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also
observed. Amyloid plaques in APOE ε3/ε3
tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and
multi-lobulated plaques with relatively smaller coronas. Despite the different
morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral
properties identical to those of APOE ε4/ε4
plaque cores. Conclusions: These data support the hypothesis that one
mechanism by which the APOE ε4 allele affects AD is by modulating
the macrostructure of pathological protein deposits in the brain. APOE ε4
is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques
arise from multiple initiation foci that coalesce as the plaques grow.