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Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs

Lauren Walker1, Kirsty E McAleese, Alan J Thomas

  • 1Institute of Neuroscience and Institute for Ageing, Newcastle University, Campus for Ageing and Vitality, NE4 5PL, Newcastle upon Tyne, UK.

Acta Neuropathologica
|March 12, 2015
PubMed

Insights

Mixed dementia pathology is common, but distinct clinical presentations correlate with varying amounts and locations of protein aggregates like tau, amyloid-β, and α-synuclein in Alzheimer's disease and Lewy body disease cases.

Area of Science:

  • Neuropathology
  • Neurodegenerative Diseases
  • Clinical Neurology

Background:

  • Mixed pathologies, including Alzheimer's disease (AD) and Lewy body disease (LBD), are common in human brains.
  • Mixed dementia diagnosis requires meeting criteria for multiple full-blown diseases, which is less frequent than mixed pathology.
  • Understanding the relationship between neuropathological findings and clinical presentation in mixed dementia is crucial.

Purpose of the Study:

  • To quantitatively measure hyperphosphorylated tau (HP-τ), amyloid-β (Aβ), and α-synuclein (α-syn) in mixed AD/LBD cases.
  • To compare protein aggregate loads and distributions across different clinical phenotypes (AD, DLB, PDD) within mixed pathology.
  • To investigate clinicopathological correlations in mixed neurodegenerative diseases.

Main Methods:

  • Quantitative measurement of HP-τ, Aβ, and α-syn using immunopositivity and image analysis on brain sections.
  • Study included 28 cases with neuropathological mixed AD/DLB diagnosis, categorized by clinical presentation (cAD, cDLB, cPDD).
  • Comparison with pure AD and pure DLB cases.

Main Results:

  • Clinically diagnosed AD (cAD) cases showed higher HP-τ loads compared to cDLB and cPDD.
  • HP-τ distribution in cAD resembled pure AD, while cDLB had less hippocampal HP-τ.
  • cPDD cases exhibited lower HP-τ and Aβ loads, but higher α-syn loads.

Conclusions:

  • The amount and topographical distribution of pathological protein aggregates differ based on clinical phenotypes in mixed AD/DLB.
  • Quantitative clinicopathological studies are essential for understanding the neuropathological basis of clinical symptoms in mixed dementia.
  • Further research is warranted to elucidate the complex interplay between mixed pathologies and clinical manifestations.

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