Objectives: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral β-amyloid (Aβ) protein deposition, neurodegeneration of AD-signature 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 [11C] Pittsburgh compound B-PET, 18F-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). Aβ 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 Aβ deposition and Aβ positivity. The low albumin group showed a significantly higher Aβ 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.