Accumulation of cellular prion protein within dystrophic neurites of amyloid plaques in the Alzheimer's disease brain.

Abstract

Amyloid plaques, a well-known hallmark of Alzheimer's disease (AD), are formed by aggregated β-amyloid (Aβ). The cellular prion protein (PrPc) accumulates concomitantly with Aβ in amyloid plaques. One type of amyloid plaque, classified as a neuritic plaque, is composed of an amyloid core and surrounding dystrophic neurites. PrPc immunoreactivity reminiscent of dystrophic neurites is observed in neuritic plaques. Proteinase K treatment prior to immunohistochemistry removes PrPc immunoreactivity from amyloid plaques, whereas Aβ immunoreactivity is enhanced by this treatment. In the present study, we used a chemical pretreatment by a sarkosyl solution (0.1% sarkosyl, 75 mM NaOH, 2% NaCl), instead of proteinase K treatment, to evaluate PrPc accumulation within amyloid plaques. Since PrPc within amyloid plaques is removed by this chemical pretreatment, we can recognize that the PrP species deposits within amyloid plaques were PrPc. We could observe that PrPc accumulation in dystrophic neurites occurred differently compared with Aβ or hyperphosphorylated tau aggregation in the AD brain. These results could support the hypothesis that PrPc accumulation in dystrophic neurites reflects a response to impairments in cellular degradation, endocytosis, or transport mechanisms associated with AD rather than a non-specific cross-reactivity between PrPc and aggregated Aβ or tau.

• Authors: Reisuke H Takahashi, Minoru Tobiume, Yuko Sato, Tetsutaro Sata, Gunnar K Gouras, Hidehiro Takahashi
• Journal: Neuropathology : official journal of the Japanese Society of Neuropathology (Neuropathology) Vol. 31 Issue 3 Pg. 208-14 (Jun 2011) ISSN: 1440-1789 [Electronic] Australia
• PMID: 21062360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Japanese Society of Neuropathology.

Chemical References

• Amyloid beta-Peptides
• PrPC Proteins
• tau Proteins

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (immunology, metabolism)
• Blotting, Western
• Cross Reactions
• Humans
• Immunohistochemistry
• Neurites (metabolism, pathology)
• Plaque, Amyloid (metabolism, pathology)
• PrPC Proteins (immunology, metabolism)
• tau Proteins (immunology, metabolism)