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P4‐010: THE 100‐PLUS STUDY: WHAT THE OLDEST‐OLD CAN TEACH US
Author(s) -
Holstege Henne,
Wemmenhove Elizabeth,
Sistermans Erik,
Reinders Marcel J.T.,
MeijersHeijboer Hanne,
Scheltens Philip
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1524
Subject(s) - dementia , cognitive decline , cognition , heredity , life expectancy , gerontology , medicine , pathological , psychology , psychiatry , biology , pathology , genetics , disease , population , environmental health
approach. The genotype data were linked to the age of cognitive decline, estimated as the age at which symptoms of progressive decline were first observed. Kaplan-Meier survival estimates were obtained to test for associations between cognitive decline and APOE and TOMM40 polymorphisms. Results: LD between TOMM40 poly-T lengths of 20 to 29 bases and APOE-e4 was unequivocally shown. Both APOE (p<0.0001) and TOMM40 (p<0.0001) described significant variation in decline, occurring earliest for APOEe4/e4 and TOMM40 poly-T 20-29/20-29. Intermediate cognitive decline was observed for those with a single APOEe4 allele or single poly-T 20-29 TOMM40. Interestingly, the length of TOMM40 poly-T in cases of APOE-e4/e4 was non-random, as no subject with poly-T lengths between 20 and 29 had poly-T lengths of 23-25. Conclusions: Our results demonstrate the tight LD between APOE and TOMM40 polymorphisms and the influence of these polymorphisms on memory decline during aging. The TOMM40 poly-T length may be important in determining TOMM40 protein expression and mitochondrial function, and we hypothesize that 23-25 poly-T lengths may be most damaging to mitochondria.