Metabolic syndrome (MetS) is associated with dementia, but it is unclear whether MetS is related to Alzheimer's disease (AD). We investigated the association of MetS with brain amyloid, a key AD feature, and neurodegeneration. A community-based sample of 350 middle-aged Hispanics in New York City had cerebral amyloid β (Aβ) burden ascertained with ¹⁸F-Florbetaben positron emission tomography. Neurodegeneration was ascertained as cortical thickness in AD signature regions from 3T brain MRI. MetS and its components (glucose, blood pressure, triglycerides, high-density lipoprotein, adiposity) were defined using the National Institutes of Health criteria. Neither the presence of MetS nor the MetS score was associated with Aβ or neurodegeneration. Among the MetS components, elevated glucose was associated with lower Aβ burden, and this association was not explained by diabetes treatment. Glucose and triglycerides were related to smaller cortical thickness. Our findings suggest that MetS as an arbitrary measure of aggregate metabolic and vascular risk does not capture the risk of AD neuropathology in late middle age and that other approaches to measure the aggregate risk should be examined.