%0 Journal Article %T Alzheimer¡¯s Disease A<i>¦Â</i>-Amyloid Plaque Morphology Varies According to <i>APOE</i> Isotype %A Ina Caesar %A K. Peter R. Nilsson %A Per Hammarstr£¿m %A Mikael Lindgren %A Stefan Prokop %A James Schmeidler %A Vahram Haroutunian %A David M. Holtzman %A Patrick R. Hof %A Sam Gandy %J World Journal of Neuroscience %P 118-133 %@ 2162-2019 %D 2023 %I Scientific Research Publishing %R 10.4236/wjns.2023.133008 %X Background: The apolipoprotein E (APOE, gene; apoE, protein) ¦Å4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer¡¯s disease (AD). Each APOE ¦Å4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ¦Å3. 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 ¦Å3 or APOE ¦Å4. Results: As expected APOE ¦Å4/¦Å4 tissues had a significantly larger load of CAA than APOE ¦Å3/¦Å3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ¦Å3/¦Å3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ¦Å4/¦Å4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ¦Å3/¦Å3 amyloid plaque cores had spectral properties identical to those of APOE ¦Å4/¦Å4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ¦Å4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ¦Å4 is associated with a higher density of amyloid plaques (as compared to APOE ¦Å3). We speculate that multilobulated APOE ¦Å4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow. %K Alzheimer¡¯s Disease %K Amyloid %K Apolipoprotein %K Luminescent Conjugated Oligothiophenes %K Hyperspectral Separation %U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=126804