Objectives: To determine if apolipoprotein E 4 influences the frequency of Alz heimer type pathologic features in tauopathies, synucleinopathies, and frontote mporal degeneration and to determine if the frequency of A...Objectives: To determine if apolipoprotein E 4 influences the frequency of Alz heimer type pathologic features in tauopathies, synucleinopathies, and frontote mporal degeneration and to determine if the frequency of Alzheimer type patholo gic features in synucleinopathies is similar to the frequency of such features i n tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and tr ansitional Lewy body disease, frontotemporal degeneration, progressive supranucl ear palsy, corticobasal degeneration, and multiple system atrophy, with a mean a ge of 75.1 ±.9.3 years, were suitable for genetic and pathological analysis. Di sorders were grouped as tauopathies (progressive supranuclear palsy and corticob asal degeneration), synucleinopathies (Lewy body disease and multiple system atr ophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of conc omitant Alzheimer type pathologic features in each case, and apolipoprotein E g enotype was determined from DNA isolated from frozen brain tissue. The relations hip of apolipoprotein E 4 to Alzheimer type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E 4 and older a ge independently predicted the co occurrence of Alzheimer type pathologic feat ures (P<.001), whereas female sex had a lesser effect (P = .03). When divided in to the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degenerat ion), apolipoproteinE 4 had a similar effect, whereas older age and female sex w ere less predictive. There was a significant difference between the frequency of Alzheimer type pathologic features in synucleinopathies and the frequency of s uch features in tauopathies and frontotemporal degeneration (P<.001 for both). T he frequency of apolipoprotein E 4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E 4, independent of older age and sex, contributes to the co occurrence of Alzheimer type pathologic features in tau opathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal d egeneration.展开更多
文摘Objectives: To determine if apolipoprotein E 4 influences the frequency of Alz heimer type pathologic features in tauopathies, synucleinopathies, and frontote mporal degeneration and to determine if the frequency of Alzheimer type patholo gic features in synucleinopathies is similar to the frequency of such features i n tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and tr ansitional Lewy body disease, frontotemporal degeneration, progressive supranucl ear palsy, corticobasal degeneration, and multiple system atrophy, with a mean a ge of 75.1 ±.9.3 years, were suitable for genetic and pathological analysis. Di sorders were grouped as tauopathies (progressive supranuclear palsy and corticob asal degeneration), synucleinopathies (Lewy body disease and multiple system atr ophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of conc omitant Alzheimer type pathologic features in each case, and apolipoprotein E g enotype was determined from DNA isolated from frozen brain tissue. The relations hip of apolipoprotein E 4 to Alzheimer type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E 4 and older a ge independently predicted the co occurrence of Alzheimer type pathologic feat ures (P<.001), whereas female sex had a lesser effect (P = .03). When divided in to the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degenerat ion), apolipoproteinE 4 had a similar effect, whereas older age and female sex w ere less predictive. There was a significant difference between the frequency of Alzheimer type pathologic features in synucleinopathies and the frequency of s uch features in tauopathies and frontotemporal degeneration (P<.001 for both). T he frequency of apolipoprotein E 4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E 4, independent of older age and sex, contributes to the co occurrence of Alzheimer type pathologic features in tau opathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal d egeneration.
