Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

Area of Science:

• Neuroscience
• Neuropathology
• Biochemistry

Background:

• Prion diseases (PrionD) and Alzheimer disease (AD) are distinct neurodegenerative disorders.
• Overlap in pathological changes between PrionD and AD suggests potential shared mechanisms.

Purpose of the Study:

• To investigate mechanistic links between PrionD and AD.
• To determine if PrionD can induce AD-like pathology, specifically beta-amyloid (Aβ) and tau.
• To explore the role of scrapie-associated prion protein (PrP) and apolipoprotein E-4 (APOE-4) in PrionD-associated neurodegeneration.

Main Methods:

• Analysis of brain tissue from 266 patients with PrionD and 6 controls.
• In vitro exposure of human brain aggregates (BrnAggs) to Creutzfeldt-Jakob disease (CJD) brain homogenate.
• Western blot analysis to quantify Aβ42 levels.
• Immunohistochemical examination of hippocampal CA1 regions for PrP, Aβ42, APOE-4, and hyperphosphorylated tau (Hτ).

Main Results:

• 17% of PrionD patients exhibited AD-like changes.
• CJD-infected BrnAggs produced abundant intraneuronal Aβ42 inclusions, unlike controls.
• Western blots confirmed higher Aβ42 levels in CJD-infected aggregates.
• Hippocampal analysis revealed distinct patient subgroups based on PrP and Aβ42 levels, with high PrP and APOE-4 correlating with significant neuron loss.
• Both PrionD and AD groups showed increased Hτ pathology.

Conclusions:

• Prion disease can induce biochemical changes mirroring those in Alzheimer disease.
• PrionD pathogenesis involves PrP, Aβ42, APOE-4, and abnormal tau.
• The findings suggest PrionD may act as a trigger for AD-like pathology.