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P3–193: Genotype–phenotype relationship is lacking in families with PS1–Met146Leu founder mutation
Author(s) -
Bruni Amalia C.,
Terni Beatrice,
Bernardi Livia,
Tomaino Carmine,
Maletta Raffaele,
Smirne Nicoletta,
Calignano Cinzia,
Paonessa Annamaria,
Leotta Attilio,
Santo Lio,
Puccio Gianfranco,
Colao Rosanna,
Frangipane Francesca,
Curcio Sabrina A.M.,
Mirabelli Maria,
Hachimi Hamid El.,
Foncin Jean F.,
Grazia Spillantini Maria
Publication year - 2006
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.2006.05.1461
Subject(s) - immunohistochemistry , neuropil , pathology , cortex (anatomy) , senile plaques , biology , neuropathology , tau protein , antibody , staining , microbiology and biotechnology , alzheimer's disease , genetics , medicine , disease , neuroscience , central nervous system
and other pathologies in clinically demented and non-demented individuals, although its exact contributions to etiology and clinical expression remain unclear. The NACC neuropathology data are gathered from 30 Alzheimer’s Disease Centers funded by the National Institute on Aging. Objective(s): To describe the occurrence of LB pathology at postmortem study by clinical diagnoses for demented and non-demented NACC database subjects who died between 1999 and 2005. Methods: We used NACC data from individuals with a clinical dementia diagnosis or who were clinically non-demented, who had died between 1999 and 2005, and who received neuropathological examination including assessment of LB pathology (N 3660). Before the late 1990s, LB pathology was likely incompletely assessed until the use of ubiquitin and -synuclein stains became widely available. However, a NACC survey indicated that 90% and 80% of ADCs were using -synuclein or ubiquitin immunohistochemistry, respectively, after 1999. LB pathology was categorized as (1) brainstem predominant; (2) transitional/limbic; (3) diffuse neocortical; (4) unspecified type; or (5) no LB. Cases recorded as “not assessed”, unknown or missing were excluded. Results: LB pathology was recorded in 29%, 32%, and 30% of clinically diagnosed Probable AD, Possible AD and Non-AD dementias, respectively. Across those same diagnostic categories, “diffuse neocortical” LB pathology was the most frequent type, occurring in 11%, 17% and 16%, respectively. LB pathology occurred proportionally more with increasing Braak stage: Braak 0; 18%, I-II: 24%; III-IV: 33%; V-VI; 28%. [p(trend) 0.01]. Among persons with a clinical diagnosis of DLB (with or without probable AD) (n 268), 41% had diffuse neocortical LB and 31% had no LB pathology. Conversely, among individuals without clinically diagnosed DLB (n 3392), 8.6% had diffuse neocortical LB, while 76% had no LB pathology. Conclusions: The large numbers of subjects included in the NACC database allow patterns of LB pathology to be observed. LB pathology appears commonly in both clinically diagnosed AD and non-AD dementias (including clinically unrecognized DLB cases); within LB pathology categories, diffuse neocortical type predominates. LB pathology and Braak stage were significantly associated; possibly resulting from an association between tau protein and alpha-synuclein.