Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes.

Abstract

We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many β-amyloid (Aβ; Aβ42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease-infected BrnAggs verified Aβ42 levels higher than those in controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrP), many Aβ42 intraneuronal inclusions, low apolipoprotein E-4 (APOE-4), and no significant nerve cell loss. Seven patients had high levels of PrP, low Aβ42, high APOE-4, and 40% nerve cell loss, suggesting that APOE-4 and PrP together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (Hτ) and Hτ-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain Aβ42 deposits; however, there were rare Hτ-positive threads in 5 controls, and 2 controls had few Hτ-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to those triggered by AD and suggest that PrionD is a disease involving PrP, Aβ42, APOE-4, and abnormal tau.

• Authors: Thomas Tousseyn, Krystyna Bajsarowicz, Henry Sánchez, Ania Gheyara, Abby Oehler, Michael Geschwind, Bernadette DeArmond, Stephen J DeArmond
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 74 Issue 9 Pg. 873-88 (Sep 2015) ISSN: 1554-6578 [Electronic] England
• PMID: 26226132 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Topics

• Aged
• Alzheimer Disease (genetics, pathology)
• Animals
• Brain (pathology)
• Female
• Humans
• Male
• Mice
• Mice, Transgenic
• Middle Aged
• Prion Diseases (genetics, pathology)