To examine the ability to detect concurrent Lewy Body (LB) pathology in Autosomal Dominant Alzheimer’s Disease (AD) through detection of misfolded alpha-synuclein in CSF using a seed amplification assay (SAA).

Neuropathological studies have shown that LB pathology is present in about 50% of cases of sporadic AD and about 30% of Autosomal Dominant AD. Clinical recognition of concurrent LB and AD pathologies in patients is crucial as the presence of both predicts a faster rate of cognitive decline, need to treat additional parkinsonian motor and non-motor symptoms, and a less predictable response to both symptomatic and disease modifying treatments.   

We collected clinical, cerebrospinal fluid (CSF), and post-mortem neuropathological data from 31 individuals within families with confirmed Autosomal Dominant AD due to mutations in either PSEN1 or APP. Twenty-two individuals were mutation carriers and 9 were non-carriers. We examined the prevalence of alpha-synuclein SAA positivity in CSF from these individuals. We correlated this data with their clinical presentation and post-mortem neuropathological data.

Of the 22 mutation carriers, 4 (18%) showed positive alpha-synuclein seeding activity. Of the 9 non-carriers, none showed seeding activity. Of the 4 mutation carriers with positive seeding activity, two were asymptomatic, one was mildly symptomatic (Mild Cognitive Impairment, CDR 0.5), and one had mild dementia (CDR 1). Among the 22 mutation carriers, we found no association between alpha-synuclein reactivity and UPDRS III score nor dream enactment behavior.