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An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices
Published on: April 11, 2018
Neuropathological alterations in Alzheimer disease
Alberto Serrano-Pozo1, Matthew P Frosch, Eliezer Masliah
1Alzheimer Research Unit of the MassGeneral Institute for Neurodegenerative Disease, Department of Neurology of the Massachusetts General Hospital, and Harvard Medical School, Charlestown, Massachusetts, USA, 02129-4404.
Cold Spring Harbor Perspectives in Medicine
|January 10, 2012
Summary
Alzheimer disease (AD) pathology, including amyloid plaques and neurofibrillary tangles, progresses over time and correlates with cognitive decline. In vivo imaging validates these neuropathological findings in Alzheimer disease.
Area of Science:
- Neuropathology
- Neurodegenerative Diseases
- Alzheimer Disease Research
Background:
- Alzheimer disease (AD) is characterized by neuropathological hallmarks including amyloid plaques, neurofibrillary tangles, and neuronal/synaptic loss.
- Postmortem studies have historically staged AD progression, informing diagnostic criteria.
- Clinicopathological studies reveal a continuum from normal aging to AD dementia.
Purpose of the Study:
- To summarize the progression of Alzheimer disease neuropathology.
- To correlate neuropathological findings with cognitive decline.
- To validate postmortem findings with in vivo imaging biomarkers.
Main Methods:
- Analysis of cross-sectional postmortem neuropathological data.
- Clinicopathological correlation studies.
- Validation using longitudinal in vivo imaging studies (amyloid PET, volumetric MRI).
Main Results:
- Amyloid plaque accumulation precedes cognitive deficits in Alzheimer disease.
- Neurofibrillary tangles, neuronal loss, and synaptic loss parallel cognitive decline.
- In vivo imaging biomarkers confirm the progression patterns observed in postmortem studies.
Conclusions:
- Neuropathological hallmarks of Alzheimer disease follow a predictable progression.
- Synaptic loss is a key correlate of cognitive decline in AD.
- Modern imaging techniques validate established neuropathological staging of Alzheimer disease.
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