Biochemical staging of synucleinopathy and amyloid deposition in dementia with Lewy bodies.
J Neuropathol Exp Neurol
; 65(3): 278-88, 2006 Mar.
Article
en En
| MEDLINE
| ID: mdl-16651889
ABSTRACT
The primary feature of dementia with Lewy bodies (DLB) is the aggregation of alpha-synuclein into characteristic lesions Lewy bodies (LBs) and Lewy neurites. However, in most of DLB cases, LBs are associated with neurofibrillary tangles and amyloid plaques (both Alzheimer disease [AD]-related lesions). We wanted to determine if this overlap of lesions is statistical, as a result of the late onset of both diseases, or results from a specific physiopathological synergy between synucleinopathy and either tauopathy or amyloid pathology. All patients with DLB from our prospective and multidisciplinary study were analyzed. These cases were compared with cases with pure AD and patients with Parkinson disease and controls. All cases were analyzed thoroughly at the neuropathologic and biochemical levels with a biochemical staging of aggregated alpha-synuclein, tau, and Abeta species. All sporadic cases of DLB were associated with abundant deposits of Abeta x-42 that were similar in quality and quantity to those of AD. Amyloid precursor protein (APP) dysfunction is a risk factor for AD as demonstrated by pathogenic mutations and Abeta accumulation. The constant and abundant Abeta x-42 deposition in sporadic DLB suggests that synucleinopathy is also promoted by APP dysfunction. Therefore, we conclude that APP is a therapeutic target for both AD and DLB.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Precursor de Proteína beta-Amiloide
/
Enfermedad por Cuerpos de Lewy
/
Alfa-Sinucleína
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia