Table 4 Studies investigating the effects of APOE4 on amyloid plaques in AD patients

Tiraboschi et al. [93]

296 AD autopsy cases were evaluated for amyloid plaques and NFTs in the hippocampus, and midfrontal, inferior parietal, and superior temporal cortices.

Mean age at death of APOE4+ homozygotes was 76.4 (n = 38; 55% female), APOE+ heterozygotes was 80.1 (n = 149; 54% female), and APOE4− was 80.2 (n = 109; 58% female). No ancestry information was provided.

APOE4/4 AD patients demonstrated significantly more amyloid plaques and NFTs in neocortical regions than APOE3/4 or APOE4− AD patients.

Drzezga et al. [81]

32 moderate AD patients matched for demographic and cognitive impairment were evaluated for amyloid plaque deposition via PIB-PET imaging.

Mean age for APOE4+ AD patients was 67 (n = 18; 50% female) and APOE4− AD patients was 68 (n = 14; 35% female). No ancestry information was provided.

APOE4+ AD patients exhibited significantly higher and more extended amyloid plaque deposition, especially in bilateral prefrontal and temporoparietal cortex compared to APOE4− AD patients.

Berg et al. [94]

186 AD autopsy cases and 13 controls were evaluated for multiple brain histological markers of AD, including brain densities of amyloid plaques and NFTs.

Broken down by CDR, the mean age at death of CDR = 0 was 82.4 (n = 13; 38% female), CDR = 0.5 was 88.6 (n = 17; 52% female), CDR = 1 was 87.8 (n = 8; 50% female), CDR = 2 was 81.2 (n = 17; 52% female), and CDR = 3 was 79.8 (n = 144; 55% female). No ancestry information was provided.

Controlling for dementia severity, plaque densities were weakly associated with APOE4 status in the hippocampus. The degree of CAA was more strongly associated with APOE4 status.

Rowe et al. [95]

53 mild AD, 57 MCI, and 177 control cases (AIBL cohort) were evaluated for amyloid plaque deposition via PIB-PET imaging.

Mean age of AD patients was 72.6 (n = 53; 56% female), MCI patients was 75.5 (n = 57; 49 female), and controls was 71.6 (n = 177; 49% female). No ancestry information was provided.

APOE4+ MCI patients and controls exhibited statistically higher PIB binding than APOE4− MCI patients and controls. However, there were no differences observed between APOE4+ vs. APOE4− AD patients.

Landen et al. [96]

44 AD, 11 vascular dementia, and 29 age-matched control autopsy cases were evaluated for amyloid plaques and NFTs in the hippocampus and frontal cortex.

Mean age at death for APOE4+ AD patients was 78.1 (n = 32), APOE4− AD patients was 82.5 (n = 12), APOE4+ VaD patients was 76.7 (n = 3), APOE4− VaD patients was 80.1 (n = 8), and APOE4+ controls was 71.0 (n = 19), APOE4− controls was 75.7 (n = 10). AD patients were 61% female, VaD patients were 27% female, and controls were 34% female. No ancestry information was provided.

No association was found between APOE4 status and amyloid plaque or NFT levels in either the AD, vascular dementia, or control groups.

Ossenkoppele et al. [97]

22 APOE4− AD patients, 40 APOE3/4 AD patients, and 22 APOE4/4 AD patients were evaluated for amyloid plaques and brain metabolism using PIB-PET and FDG-PET, respectively.

Mean age of APOE4+ homozygotes was 65 (n = 22; 41% female), APOE4+ heterozygotes was 62 (n = 40; 38% female), and APOE4− was 61 (n = 22; 27% female). No ancestry information was provided.

APOE4− AD patients exhibited increased PIB binding in the frontal cortex compared to APOE4+ AD patients, while APOE4− AD patients had less profound metabolic impairment in the posterior parts of the cortex compared to APOE4+ AD patients.

Lehmann et al. [98]

52 probable AD and 52 control cases were evaluated for amyloid plaque deposition and brain metabolism using PIB-PET and FDG-PET, respectively.

Mean age for APOE4+ AD patients was 64.3 (n = 23; 48% female), APOE4− AD patients was 62.7 (n = 29; 41% female), and controls was 72.3 (n = 52; 58% female). No ancestry information was provided.

APOE4− AD patients exhibited increased global amyloid plaque burden compared to matched APOE4+ AD patients. In contrast, APOE4+ AD patients exhibited greater medial temporal hypometabolism compared to APOE4− AD patients.