Choroid Plexus Calcification Associations with Brain Morphology and Family History of Alzheimer's Disease

Abstract

AbstractBackgroundThe choroid plexus (CP) is the primary source of cerebrospinal fluid (CSF) production and forms the blood‐CSF barrier which regulates nutrients and hormones to the brain. Changes in CSF production are associated with aging and Alzheimer’s disease (Saade 2019, Hubert 2019). CP calcification (CPcal) has been associated with metabolic disorders, cerebrovascular diseases, and tumors (Wu, 2009). Here, we used MRI‐derived quantitative susceptibility mapping (QSM) from the UK Biobank(Miller, 2016) to investigate whether CPcal is associated with morphological brain alterations and family history of Alzheimer's disease or related dementias (ADRD).MethodWe analyzed susceptibility weighted images (SWI) from 32,426 participants (aged 45‐83 years, F = 54%) from the UK Biobank, and 1716 follow‐up scans (aged 50‐83 years, F = 53%) Table 1. CPcal volumes were extracted from processed QSM maps (Figure 1) within FreeSurfer‐defined brain ventricles: total, lateral (LV), third (3rdV), and fourth ventricle (4thV). 34 regional cortical thickness and surface area measures, and 11 subcortical volumes were extracted using FreeSurfer. Linear regressions were used to assess the relationship between log‐transformed CPcal volumes and cross‐sectional and longitudinal change in FreeSurfer brain metrics (tp2‐tp1/tp1) adjusting for age, sex, LV and intracranial volumes. The false discovery rate (FDR, q=0.05) was applied to adjust for multiple comparisons across brain regions. Linear regression was used to investigate whether CPcal volumes were associated with family history of AD or dementia.ResultGreater CPcal volumes were associated with regional brain morphometry, cross sectionally, and longitudinally (Figure 2). Total CPcal were associated with family history of AD; specifically maternal history of AD showed a stronger association with total CPcal while paternal history showed no association (Table 2).ConclusionUsing QSM, we show that CP calcification impacts structural brain measures and is associated with family history of ADRD. This suggests that CPcal may be an important biomarker for tracking age related changes and AD, and may be an important biomarker for imaging genetic studies.