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Thinking outside the box: Alzheimer-type neuropathology that does not map directly onto current consensus
Peter T Nelson1, Walter A Kukull, Matthew P Frosch
1Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536-0230, USA. pnels2@email.uky.edu
Journal of Neuropathology and Experimental Neurology
|April 27, 2010
Summary
Neuropathologists struggle to classify some dementia cases. This study found "tangle-intensive" brains were more often linked to Alzheimer's disease than "plaque-intensive" ones.
Area of Science:
- Neuropathology
- Neurodegenerative Diseases
- Alzheimer's Disease Research
Background:
- Existing neuropathologic diagnostic guidelines, such as those from the National Institute on Aging and Reagan Institute, may not explicitly categorize all cognitively impaired patient brains.
- Specific challenging cases include "tangle-intensive" brains with high neurofibrillary tangle density and moderate amyloid plaques, and "plaque-intensive" brains with intermediate tangles and high amyloid plaques.
- Understanding these unclassifiable cases is crucial for accurate Alzheimer's disease diagnosis.
Purpose of the Study:
- To analyze neuropathologic and clinical data from a large registry of dementia cases.
- To evaluate how neuropathologists at Alzheimer Disease Centers diagnose "plaque-intensive" and "tangle-intensive" cases.
- To identify potential improvements in diagnostic categories for Alzheimer's disease.
Main Methods:
- Analysis of 1,677 cases with antemortem dementia diagnoses from the National Alzheimer's Coordinating Center Registry.
- Inclusion of both clinical and pathological data from National Institute on Aging-funded Alzheimer Disease Centers.
- Assessment of diagnostic tendencies for plaque-intensive and tangle-intensive cases based on neuropathologist evaluations.
Main Results:
- Tangle-intensive cases were more frequently diagnosed as having a "high likelihood" of Alzheimer's disease.
- Plaque-intensive cases were more often designated as having an "intermediate likelihood" of Alzheimer's disease.
- Only at Braak Stage VI did tangle-intensive cases show significantly lower Mini-Mental State Examination scores compared to plaque-intensive cases (p < 0.02).
Conclusions:
- Current diagnostic categories may not fully encompass the spectrum of Alzheimer's disease neuropathology.
- Explicit diagnostic criteria and a deeper understanding of early-phase Alzheimer's pathology are needed.
- Improved diagnostic guidance can aid neuropathologists in classifying complex dementia cases.
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