Frequency and Clinicopathological Characteristics of Presenilin 1 Gly206Ala Mutation in Puerto Rican Hispanics with Dementia

Article type: Research Article

Authors: Arnold, Steven E.^{a; b; *} | Vega, Irving E.^c | Karlawish, Jason H.^d | Wolk, David A.^b | Nunez, Jessica^a | Negron, Mirna^a | Xie, Sharon X.^e | Wang, Li-San^f | Dubroff, Jacob G.^g | McCarty-Wood, Elisabeth^f | Trojanowski, John Q.^f | Van Deerlin, Vivianna^f

Affiliations: [a] Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA | [b] Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA | [c] Department of Biology, University of Puerto Rico, Rio Piedras, San Juan, PR, USA | [d] Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA | [e] Department of Biostatistics, University of Pennsylvania, Philadelphia, PA, USA | [f] Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA | [g] Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Steven E. Arnold, M.D., Penn Memory Center, University of Pennsylvania, 3615 Chestnut Street, Philadelphia, PA 19104, USA. Tel.: +1 215 349 8225; Fax: +1 215 349 8540; E-mail: [email protected]; Administrative Assistant: Maria Crudele, Tel.: +1 215 349 8225; [email protected].

Abstract: The frequency and clinical and pathological characteristics associated with the Gly206Ala presenilin 1 (PSEN1) mutation in Puerto Rican and non-Puerto Rican Hispanics were evaluated at the University of Pennsylvania's Alzheimer's Disease Center. DNAs from all cohort subjects were genotyped for the Gly206Ala PSEN1 mutation. Carriers and non-carriers with neurodegenerative disease dementias were compared for demographic, clinical, psychometric, and biomarker variables. Nineteen (12.6%) of 151 unrelated subjects with dementia were discovered to carry the PSEN1 Gly206Ala mutation. Microsatellite marker genotyping determined a common ancestral haplotype for all carriers. Carriers were all of Puerto Rican heritage with significantly younger age of onset, but otherwise were clinically and neuropsychologically comparable to those of non-carriers with AD. Three subjects had extensive topographic and biochemical biomarker assessments that were also typical of non-carriers with AD. Neuropathological examination in one subject revealed severe, widespread plaque and tangle pathology without other meaningful disease lesions. The PSEN1 Gly206Ala mutation is notably frequent in unrelated Puerto Rican immigrants with dementia in Philadelphia. Considered together with the increased prevalence and mortality of AD reported in Puerto Rico, these high rates may reflect hereditary risk concentrated in the island which warrants further study.

Keywords: Age of onset, dementia, haplotype, presenilin

DOI: 10.3233/JAD-2012-121570

Journal: Journal of Alzheimer's Disease, vol. 33, no. 4, pp. 1089-1095, 2013