Serum albumin and beta-amyloid deposition in the human brain

Objectives To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral beta-amyloid (A beta) protein deposition, neurodegeneration of ADsignature regions, and cerebral white matter hyperintensities (WMH), in the human brain. Methods A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [C-11] Pittsburgh compound B-PET, F-18-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.4 g/dL (low albumin), 4.4 to 4.5 g/dL (middle albumin), and >4.5 g/dL (high albumin; used as a reference category). A beta positivity, AD-signature region cerebral glucose metabolism (AD-CM), AD-signature region cortical thickness (AD-CT), and WMH volume were used as outcome measures. Results Serum albumin level (as a continuous variable) was inversely associated with A beta deposition and A beta positivity. The low albumin group showed a significantly higher A beta positivity rate compared to the high albumin group (odds ratio 3.40, 95% confidence interval 1.67-6.92, p = 0.001), while the middle albumin group showed no difference (odds ratio 1.74, 95% confidence interval 0.80-3.77, p = 0.162). Neither serum albumin level (as a continuous variable) nor albumin categories were related to AD-CM, AD-CT, or WMH volume. Conclusions Low serum albumin may increase the risk of AD dementia by elevating amyloid accumulation. In terms of AD prevention, more attention needs to be paid to avoid a low serum albumin level, even within the clinical normal range, by clinicians.