Amyloid-Mediated Cholinergic Dysfunction in Motor Impairment Related to Alzheimer's Disease

Tommaso Schirinzi, Francesco Di Lorenzo, Giulia Maria Sancesario, Giulia Di Lazzaro, Viviana Ponzo, Antonio Pisani, Nicola Biagio Mercuri, Giacomo Koch, Alessandro Martorana

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Although motor disturbances parallel the course of dementia, worsening both quality of life and social costs, the pathogenesis remains still unclear. Objective: Through the combination of cerebrospinal fluid (CSF) biomarkers assessment and transcranial magnetic stimulation (TMS) protocols, here we provided a cross-sectional study to understand pathogenic mechanisms of Alzheimer's disease (AD)-related early motor disturbances. Methods: The motor phenotype, as defined with Unified Parkinson's Disease Rating Scale (UPDRS) part 2-3, Rating Scale for Gait Evaluation in Cognitive Deterioration (RSEGCD) and Tinetti scale, together with CSF profile of amyloid-β 42 (Aβ 42), total-tau, and phosphorylated-tau were determined in 37 AD patients and compared to 18 patients with vascular dementia (VaD). A TMS protocol of short afferent inhibition (SAI) was further applied on a subset of AD patients. Clinical, biochemical, and neurophysiological data were then compared and correlated in order to find significant associations. Results: AD patients exhibited subtle locomotor impairment and slight extrapyramidal signs. Main motor features (UPDRS part 3, RSGECD, and Tinetti scale scores) correlate with Aβ 42 levels but not with t-tau and p-tau. AD patients also presented SAI impairment directly related to UPDRS part 3 score and Aβ 42 levels. Motor disturbances of VaD group did not differ statistically from AD and did not correlate with CSF biomarkers. Conclusions: The association of motor disturbances with low Aβ 42 CSF levels and individual SAI suggests that amyloid-mediated degeneration of cholinergic system may account for early AD-related motor impairment, providing interesting insights either for frailty stratification of patients or personalized therapies.

Original languageEnglish
Pages (from-to)525-532
Number of pages8
JournalJournal of Alzheimer's Disease
Volume64
Issue number2
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Alzheimer's disease
  • amyloid
  • cholinergic
  • frailty
  • gait
  • locomotor
  • vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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