1. Biochemical Staging of Synucleinopathy and Amyloid Deposition in Dementia With Lewy Bodies
- Author
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Claude Alain Maurage, Antoine Ghestem, S. Bombois, Hervé Drobecq, Vincent Deramecourt, Florence Lebert, Florence Pasquier, Eugeen Vanmechelen, André Delacourte, Neuroendocrinologie et physiopathologie neuronale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Troubles cognitifs vasculaires et dégénératifs - EA 2691 (TCDV), Université de Lille, Droit et Santé, Synthèse, structure et fonction des biomolécules (SSFB), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), INNOGENETICS N.V, This work was supported by the integrated project APOPIS (Abnormal Proteins in the Pathogenesis of Neurodegenerative Disorders) funded by the European Community under the sixth framework program., and The authors thank Innogenetics for the gift of alpha-synuclein antibody Syn1b (3B5) and recombinant alpha-synuclein.
- Subjects
Male ,MESH: Lewy Body Disease/pathology ,Pathology ,Dementia with Lewy bodies ,MESH: Alzheimer Disease/pathology ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,Mass Spectrometry ,Amyloid beta-Protein Precursor ,chemistry.chemical_compound ,MESH: Aged, 80 and over ,0302 clinical medicine ,MESH: alpha-Synuclein/metabolism ,MESH: Parkinson Disease/metabolism ,Amyloid precursor protein ,Electrophoresis, Gel, Two-Dimensional ,Senile plaques ,MESH: Amyloid beta-Protein Precursor/metabolism ,Aged, 80 and over ,Cerebral Cortex ,MESH: Aged ,0303 health sciences ,MESH: Middle Aged ,biology ,MESH: Parkinson Disease/pathology ,Parkinson Disease ,MESH: tau Proteins/metabolism ,General Medicine ,Middle Aged ,MESH: Cerebral Cortex/metabolism ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,3. Good health ,Neurology ,Female ,Tauopathy ,Alzheimer disease ,Alzheimer's disease ,Lewy Body Disease ,Amyloid ,medicine.medical_specialty ,tau Proteins ,Neuropathology ,MESH: Cerebral Cortex/anatomy & histology ,Pathology and Forensic Medicine ,Alpha-synuclein ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,mental disorders ,medicine ,Humans ,MESH: Alzheimer Disease/metabolism ,Aged ,030304 developmental biology ,MESH: Mass Spectrometry ,MESH: Humans ,MESH: Lewy Body Disease/metabolism ,business.industry ,MESH: Electrophoresis, Gel, Two-Dimensional ,medicine.disease ,MESH: Male ,nervous system diseases ,chemistry ,biology.protein ,Neurology (clinical) ,MESH: Cerebral Cortex/pathology ,business ,MESH: Female ,Biomarkers ,030217 neurology & neurosurgery - 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.
- Published
- 2006
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