Characterizing choroid plexus cyst burden across the Alzheimer’s disease continuum

BACKGROUND: Choroid plexus (ChP) is responsible for producing cerebrospinal fluid, which is increasingly recognized as important in the context of aging and Alzheimer’ disease (AD). However, structural alteration (especially cystic alteration) of ChP across the pathologically confirmed AD continuum remains unclear. MATERIALS AND METHODS: All data used in this study were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Aβ and Tau PET were utilized to define the pathologically confirmed AD continuum. The number of ChP cysts on each side were counted and the largest cyst was delineated by experienced neuroradiologist using 3D T2-FLAIR images. The number of ChP cysts was further divided into four grades on each side according to the number of cysts (grade 0 = none, grade 1 = 1–5, grade 2 = 6–10, grade 3 > 10). Then, the ChP cysts rating and the largest cyst volume were compared among subjects across the pathologically confirmed AD continuum. Moreover, correlation analyses were conducted to assess the associations of cystic alteration of ChP with pathological biomarkers, and cognitive performance. RESULTS: This study included 615 individuals (mean age, 73 years ± 7.7 [SD]; 349 [57%] female), including 259 CU cognitively unimpaired controls with negative Aβ and tau (CU A-T-), 126 CU with positive Aβ, 166 mild cognitive impairment with positive Aβ (MCI A+), and 64 AD with positive Aβ. We found that ChP cyst burden exhibited a stage-specific distribution across the AD continuum (p = 0.004), with MCI A + individuals showing prominent enrichment in Grade 2, while AD A + individuals were significantly overrepresented in Grade 1. The ChP cysts rating were positively associated with age (p < 0.001). Both the ChP cysts rating and largest ChP cyst volume were associated with enlarged perivascular spaces ratings (p < 0.05). The ChP cyst indices were significantly associated with amyloid (p < 0.05). DISCUSSION: In addition to volume change, cystic alteration of the ChP may serve as a valuable neuroimaging biomarker for early diagnosing and disease progression monitoring on AD continuum. CLINICAL TRIAL REGISTRATION: Not applicable.