Title

Caspase Cleaved Tau Accumulation in Neurodegenerative Diseases is Associated with Tau and Synuclein Pathology

Publication Date

12-2004

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Biology

Department

Biology

Major Advisor

Troy Rohn

Advisor

Cheryl Jorcyk

Advisor

Julia Oxford

Abstract

Alzheimer's disease (AD), Pick's disease (PiD), dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are associated with the accumulation of tau or α-synuclein. In AD, β-amyloid (Aβ) associated caspase activation and cleavage of tau at Asp421 (ΔTau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether ΔTau accumulates in other diseases associated with tau but with less extracellular Aβ, PiD cases in comparison to those without extensive tau accumulation including frontotemporal dementia (FTLD) were studied. To examine a facet of other neurodegenerative diseases, PD and DLB cases associated with intracellular α-synuclein were investigated. ΔTau was observed in all disease cases except FTLD and controls. The extent of ΔTau labeling was correlated with AT8, an early tangle marker, and PHF-1, a late tangle marker, but not Aβ immunoreactivity. These results demonstrate that the accumulation of ΔTau may represent a common pathway associated with abnormal accumulation of intracellular tau or synuclein and may be relatively less dependent on the extracellular accumulation of Aβ in non-AD dementias.

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