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Comorbidities.

Irina Alafuzoff¹, Gabor G Kovacs²

¹Department of Immunology, Genetics and Pathology, Uppsala University, Department of Pathology, Uppsala University Hospital and Rudbeck Laboratory, Uppsala, Sweden.

Handbook of Clinical Neurology

|October 9, 2017

Summary

Diagnosing neurodegenerative diseases requires examining mixed pathologies, not just single protein alterations. Concomitant aging-related changes significantly influence clinical presentation in conditions like Alzheimer's and Lewy body disease.

Keywords:

altered proteins hyperphosphorylated τ transactive DNA binding protein 43 vascular lesions α-synuclin β-amyloid

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Area of Science:

Neuropathology
Neurodegenerative Diseases
Clinical Phenotyping

Background:

Comorbidities, or mixed pathologies, occur when brain tissue shows multiple protein alterations.
The presence of specific pathologies like hyperphosphorylated tau (HPτ) alongside β-amyloid (Aβ) defines Alzheimer's disease (AD).
HPτ in conjunction with α-synuclein pathology indicates Lewy body disease (LBD), with HPτ considered a concomitant alteration.

Purpose of the Study:

To highlight the significance of mixed pathologies in neurodegenerative disease diagnosis.
To emphasize how concomitant pathologies can alter the clinical phenotype.
To underscore the necessity of identifying aging-related alterations alongside primary disease markers.

Main Methods:

Analysis of brain tissue (surgical or postmortem) for protein alterations.
Histopathological examination to identify specific protein aggregates (e.g., HPτ, Aβ, α-synuclein).
Correlation of observed pathologies with clinical phenotypes.

Main Results:

Mixed pathologies are common in neurodegenerative conditions.
Concomitant pathologies can modify the clinical presentation of diseases like AD and LBD.
Even sparse but multiple alterations can collectively lead to a clinical syndrome.

Conclusions:

Confirming a single pathology (e.g., AD- or LBD-related) is insufficient for diagnosis.
Investigating concomitant aging-related alterations is crucial for accurate clinical correlation.
A comprehensive neuropathological assessment is essential for understanding disease manifestation.