Abstract
Genetic variants within two distinct regions of SORL1 have recently been associated with both familial and sporadic Alzheimer disease (AD) in multiple cohorts composed of more than 6,000 individuals.1 The original report was subsequently confirmed in an independent cohort of unrelated patients with probable AD and healthy elderly control subjects from a prospective study in multiethnic communities in northern Manhattan.2 To extend these results, we investigated a series of autopsy-confirmed cases with AD (n = 103) of white, non-Hispanic origin, and compared them with controls (n = 93) from similar ethnic origins. These analyses revealed that the same alleles in a haplotype in the 5′ region of the gene and a haplotype in the same 3′ region are associated with autopsy-proven AD. ### Methods. Frozen brain tissue was obtained from 103 autopsy-confirmed cases of AD and from 17 elderly control subjects with a normal postmortem examination and without a history of dementia or another neurologic disorder. To augment the number of controls from the same ethnic background, we included 76 nondemented elderly participants who have been followed prospectively at approximately 18-month intervals as part of a study of …
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