Cerebrospinal fluid progranulin is associated with increased cortical thickness in early stages of Alzheimer's disease

Abstract

Progranulin plays an important role in neuroinflammation in Alzheimer's disease (AD) pathophysiology, being upregulated by activated microglia. This study assessed whether cerebrospinal fluid levels of progranulin correlated with structural neuroimaging measures and cognition in 122 cognitively normal individuals, 81 mild cognitive impairment, and 70 AD patients from the Alzheimer's Disease Neuroimaging Initiative. Cognitively normal subjects were classified into 3 groups using the AT(N) system, whereas all mild cognitive impairment and AD patients were A+/TN+. Correlations between progranulin with neuroanatomical measures and cognitive decline were performed within each group. Progranulin was associated with cortical thickening in parietal, occipital, and frontal regions in cognitively normal individuals with amyloid pathology. These subjects also showed cortical thickening compared with A-/TN- subjects, an effect that was partially mediated by progranulin. In addition, higher progranulin correlated with longitudinal cognitive decline. The association between progranulin and cortical thickening, together with regional "brain swelling" in A+/TN- subjects, suggests progranulin contributes to the neuroinflammatory structural changes in preclinical AD.

Keywords: Alzheimer's disease; Cerebrospinal fluid; Cortical thickness; Magnetic resonance imaging; Neuroinflammation; Progranulin.