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O4‐06‐08: A multigenerational family with inherited, pathologically confirmed Creutzfeldt‐Jakob disease unexplained by PRNP
Author(s) -
Zee Julie,
Sleegers Kristel,
Vandenberghe Rik,
Martin JeanJacques,
Engelborghs Sebastiaan,
Sciot Raf,
Mattheijssens Maria,
De Deyn Peter P.,
Van Broeckhoven Christine,
Crols Roeland
Publication year - 2009
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.2009.05.565
Subject(s) - prnp , missense mutation , dementia , genetics , disease , medicine , biology , genotype , gene , mutation , pathology
and 24 dementia with Lewy bodies (DLB). Clinical data comprised MMSE, age at death, duration of disease; neuropathology included immunohistochemistry with assessment of Lewy body and neuritic Braak stages, cortical amyloid plaque load, cerebral amyloid angiopathy, and cerebrovascular lesions (4 degrees). Results: PDD patients were significantly older than PDND (p < 0.01); DLB were slightly younger than PDD; MMSE was PDD < DLB < PDND; duration of illness DLB < PDD < PND (not significant). LB Braak scores were highest in DLB, similar in PDD and PND (5.4/4.5/4.0); neuritic Braak scores PDD < DLB < PDND (4.2/3.8/2.4). Cortical Amyloid plaque load was DLB < PDD < PDND (3.0/2.7/1.0); CAA PDD < DLB < PDND (1.6/1.3/0.2). Striatal Amyloid load in DLB, associated with neuritic Braak stages, was significantly more severe and extensive (70%) than in both PDD (20%) and PDND (only mild in 7.2%). Globus pallidus was negative. Alpha-synuclein deposits in striatum were seen in 76% DLB, 20% PDD and 10% PDND; frequency of striatal tau pathology was DLB < PDD < PDND (70/82/100% negative). Other findings: more severe LB burden in hippocampal CA2/3 area in DLB than in PDD (79 vs 26%). Significant association between cerebrovascular lesions and neuritic Braak stage was seen in PDD but not in DLB and PDND. Conclusions: These data and new amyloid imanging data support a morphologic distinction between DLB and PDD and between PDD and PDND, indicating an influence of AD-related lesions on the progression of the neurodegenerative process and, in particular, on cognitive decline in LBDs. Both these factors appear largely independent from coexisting vascular pathology, except in cases with severe cerebrovascular lesions or those related to neuritic AD pathology. Although synergistic reactions between amyloid, alpha-synuclein and tau protein have been demonstrated by both human pathology, animal models and in vitro studies, the molecular background and the pathophysiologic/clinical impact of these pathologies in LBD await further elucidation.