Progranulin and β-Amyloid Distribution: A Case Report of the Brain From Preclinical PS-1 Mutation Carrier

Background: Progranulin (PGRN) is a multifunctional growth factor that is found in many tissues. Mutations in the PGRN gene cause familial frontotemporal dementia with ubiquitin-positive inclusions. PGRN plaque-like structures have been described in Alzheimer's disease (AD), in association with beta-amyloid (A beta) plaques. Objective: To investigate PGRN and aggregated A beta immunolabeling distribution in autopsied brain tissue from the participant with confirmed PS-1 (A246E) mutation, who died prior to clinical symptom onset. Results: Immunolabeling for PGRN was positive and accumulated/formed plaque-like structures in all studied regions. These structures most frequently colocalized with A beta though there were some that did not. PGRN plaques were most dense in medial temporal and frontal regions and predominated over aggregated A beta. Conclusions: This case report illustrates PGRN accumulation and A beta aggregation in preclinical PS-1 AD case and raises the question whether this phenomenon coincides with or precedes A beta aggregation.