Presence of cerebral amyloid modulates phenotype and pattern of neurodegeneration in early Parkinson's disease.
To evaluate the frequency of cerebral amyloid in early Parkinson's disease (ePD) and provide a multimodal assessment of the influence of cerebral amyloid on disease phenotype.



We performed a multicentre cohort study of the Parkinson's Progression Markers Initiative (PPMI), including 369 drug-naïve patients with ePD and 174 healthy controls (HC). Cerebrospinal fluid (CSF) amyloid-β levels were transformed using the linear regression procedure. A cut-off of >198 pg/mL was used to define amyloid-negative (PD-) and amyloid-positive (PD+) subgroups. Grey matter (GM) density and hippocampal volume from the MRI was measured using Advanced Normalisation Tools (ANTs). We compared demographic, genetic, CSF, behavioural, functional and imaging modalities across ePD- and ePD+ groups.



We observed that 16.5% of ePD have CSF evidence of amyloidosis. PD+ was significantly older than PD-, had a higher frequency of APOE e4 alleles and all CSF measures (total-tau, phosphorylated-tau and α-synuclein) were reduced. PD+ had reduced cognitive performance relative to PD- on Symbol-Digit Matching, Verbal Category Fluency and Delayed Recall tests. Imaging analysis in a subset of individuals (PD+ =43; PD- =241) revealed overlapping GM atrophy relative to HC in medial temporal, frontal and brainstem structures. Direct comparisons revealed PD+ GM reductions predominantly located in the frontal cortex while PD- had GM reductions in subcortical structures. These observations remain when controlling for age and APOE e4 allele status.



Cerebral amyloid in ePD yields a unique phenotype across all measured modalities that is consistent with a synergistic interaction between α-synuclein and amyloid pathology. Amyloid status should be considered when screening these individuals for trials involving disease-modifying agents.
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Corey T
CT
McMillan
Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David A
DA
Wolk
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics; D000686:Amyloidosis / Q000175:diagnosis* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000175:diagnosis* / Q000235:genetics; D001931:Brain Mapping; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000235:genetics; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000235:genetics; D010641:Phenotype; D012016:Reference Values; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
D016229:Amyloid beta-Peptides; C000612345:ApoE protein, human; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)