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[P1–237]: DIFFERENTIAL ROLE OF CSF FATTY ACID BINDING PROTEIN 3, α‐SYNUCLEIN AND ALZHEIMER's DISEASE CORE BIOMARKERS IN LEWY BODY DISORDERS AND ALZHEIMER's DEMENTIA
Author(s) -
Bernardelli Alice,
Chiasserini Davide,
Biscetti Leonardo,
Eusebi Paolo,
Salvadori Nicola,
Frattini Giulia,
Simoni Simone,
De Roeck Naomi,
Tambasco Nicola,
Stoops Erik,
Vanderstichele Hugo Marcel,
Mollenhauer Brit,
Engelborghs Sebastiaan,
Calabresi Paolo,
Parnetti Lucilla,
Sepe Federica Nicoletta
Publication year - 2017
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.2017.06.057
Subject(s) - dementia with lewy bodies , cerebrospinal fluid , dementia , medicine , parkinson's disease , cohort , disease , biomarker , fatty acid binding protein , tau protein , alzheimer's disease , pathology , gastroenterology , oncology , endocrinology , biology , biochemistry , gene
Background: Accumulation of ubiquitinated proteins and UPSassociated protein is a common feature in many neurodegenerative diseases. To address the link between proteasome impairment, AD and LBD pathology, cognition decline and noncognitive symptom, the reduction of RPT6 and the alteration of the other proteasome components and activities were investigated in to identify clinico-pathological correlations, these includes: i) Possible relationships between reduction of RPT6 and the alteration of the other proteasome components and semi-quantitative scores of AD and LBD pathology in different brain areas. ii) Possible relationships between proteasome dysfunction and the cognition function and non-cognitive symptom in LBD and AD. Methods:The analysis of the relationships between non-cognitive behaviours and mood and proteasome markers were exploratory and unbiased as there were no compelling hypotheses linking them. Furthermore, due to the different regional patterns for the protein changes and the linkage of particular behavioural symptoms to a specific brain area, each brain region was analysed separately. Results:Reductions in RPT6 and proteasome activities were found to be associated with the semi-quantitative scores for plaques and neurofibrillary tangles. Semi-quantitative plaque scores were significantly predicted by RPT6 in BA9, 40 and 24. Semi-quantitative tangle scores were significantly predicted by RPT6 in BA40 and 24. Semi-quantitative a-synuclein scores were significantly predicted by RPT6 in BA9 only. Cognitive impairment was significantly predicted by RPT6 in BA9, 40 and 24. Persecution was significantly predicted by RPT6 expression in brain regions BA9 and BA40. Depression was significantly predicted by RPT6 expression in BA9. Conclusions:Our results indicated reductions in the key proteasome component RPT6 and proteasome activity. These reductions were associated with cognitive decline, non-cognitive symptoms and protein aggregates. These data suggested that the activating of the UPS could be a therapeutic target for treating DLB, PDD and AD.