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Il genotipo e4e4 è associato al rischio di demenza

Lo stato di omozigosi per e4e4 è associato ad una progressione delle lesioni della materia bianca cerebrale maggiore di quella che si osserva negli eterozigoti e nei soggetti con genotipi diversi dall'e4e4. I motivi non sono chiari anche se si può ipotizzare che il genotipo e4e4 sia associato ad alterazioni del flusso ematico secondarie alla deposizione di amiloide tra la media e l'avventizia delle arterie cerebrali di piccolo e medio calibro.

Apolipoprotein E genotype is related to progression of white matter lesion load

Godin O, Tzourio C, Maillard P, Alpérovitch A, Mazoyer B, Dufouil C.

Stroke 2009;40:3186-3190

BACKGROUND AND PURPOSE: The relationship between white matter lesions (WMLs) and the apolipoprotein E genotype has been controversial from cross-sectional studies and no longitudinal finding has been reported. We investigated whether the apolipoprotein E genotype influences baseline and evolution over 4-year follow-up of WML volumes in a population-based sample of 1779 nondemented subjects aged 65 to 80 years old at enrollment. METHODS: The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression. RESULTS: Multivariable analyses showed that epsilon4epsilon4 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the epsilon4 allele for apolipoprotein E genotype. CONCLUSION: These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia.

Stroke 2009;40:3186-3190