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P2‐240: NEUROPHYSIOLOGICAL CORRELATES OF PSEN1 MUTATION‐RELATED SPASTIC PARAPARESIS
Author(s) -
Garbin Alexander,
Kuo Yi-Ling,
Sweeney Melanie D.,
Fisher Beth E.,
Ringman John M.
Publication year - 2019
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.2019.06.2647
Subject(s) - transcranial magnetic stimulation , modified ashworth scale , spasticity , psychology , physical medicine and rehabilitation , spastic , neuroscience , white matter , medicine , audiology , magnetic resonance imaging , stimulation , cerebral palsy , radiology
and to assess their potential diagnostic accuracy in discriminating AD from HC individuals.Methods: The levels of homoand hetero-aggregates of a-syn, Ab and tau were analysed in a cohort of AD patients at early stage either with dementia or prodromal symptoms (N1⁄439) and age-matched HC (N1⁄439). All AD patients showed a typical hippocampal phenotype and received a biomarker-based diagnosis (low cerebrospinal fluid levels of Ab peptide combined with high cerebrospinal fluid concentrations of total-tau and/or phospho-tau proteins; alternatively, a positivity to cerebral amyloid-PET scan). Results: We found lower concentrations of a-syn and its heterocomplexes (i.e., a-syn/Ab and a-syn/tau) in RBCs of AD patients compared to HC. RBC a-syn/Ab as well as RBC a-syn/tau heterodimers discriminated AD participants from HC with fair accuracy (Area under receiver operating characteristic, AUROC1⁄40.76, 0.72, respectively), whereas RBC a-syn concentrations differentiated poorly the two groups (AUROC1⁄40.63). RBC Ab and RBC a-syn/Ab heterocomplex moderately correlated with CSF Ab (rs1⁄40.435 and 0.368, respectively; P1⁄40.015 and 0.042) in a subset of 32 AD patients. Conclusions: Although additional investigations are required, these data suggest a-syn heteroaggregates in RBCs as potential tool in the diagnostic work-up of early AD diagnosis. Finally, RBCs may represent interesting peripheral in vivo models of neurodegeneration since they likely to be involved in the accumulation and clearance of the misfolded proteins.