Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study

Abstract

Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer’s disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with brain MRI and neuropsychological tests for three years and underwent a second Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-ß burden was quantified by PiB standardized uptake value ratio (SUVR), and the amount of small vessel disease was quantified by number of lacune and small vessel disease score on MRI. We also measured cortical thickness. During the three years of follow-up, compared to the APOE3 homozygotes, there was less increase in PiB SUVR among APOE2 carriers (p = 0.023), while the APOE genotype did not show significant effects on small vessel disease progression. APOE2 carriers also showed less cortical thinning (p = 0.023) and a slower rate of cognitive decline (p = 0.009) compared to those with APOE3 homozygotes. Our findings suggest that, in svMCI patients, APOE2 has protective effects against amyloid-ß accumulation, cortical thinning, and cognitive decline.

Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework

“…The data show a negative association with APOE-e4 allele suggesting that it has to be considered ''frailty'' rather than a true longevity allele 166,167 . On the contrary an enrichment of APOE-e2 allele was observed in long-lived individuals 165,168,169 and this suggests a protective role of this allele supported by a positive association between APOE-e2 and healthy cognitive status 169,170 .…”

Possible positive effect of the APOE ε2 allele on cognition in early to mid-adult life

“…One ε4 allele confers a threefold increase in risk and possession of two ε4 alleles confers an over tenfold increase in risk ( Bertram et al, 2007 ). Possession of an ε2 allele has been linked with a lower risk of AD and may also slow progression of vascular cognitive impairment ( Blacker et al, 2007 , Corder et al, 1994 , Kim et al, 2017 , Talbot et al, 1994 ).…”

Apolipoprotein E isoforms differentially regulate matrix metallopeptidase 9 function in Alzheimer’s disease

“…has been shown to prevent the conversion of monomeric Aβ into oligomeric species [134], [361], which are known to induce MMP-9 levels to a greater extent than other forms of Aβ [362], and may further describe the findings in the E2FAD animals. In these secretion studies, an apoE isoform-specific influence on MMP-9 levels was more evident after stimulation/insult with PMA or Aβ-42.…”