ArticleActa neuropathologica2019
Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85.
Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Impact of aging on animal models of Parkinson's disease.Frontiers in aging neuroscience · 2022Pooled it
- APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer's disease spectrum: A retrospective observational study.European journal of nuclear medicine and molecular imaging · 2026Article
- Brain-first and body-first subtypes of Lewy body disease.Nature reviews. Neurology · 2026Review
- The prevalence of Lewy body pathology across nine international community-based cohorts.Brain : a journal of neurology · 2026Article
- Characteristics and mechanisms of cognitive impairment in Parkinson disease.Nature reviews. Neurology · 2026Review
- Immune and metabolic signatures characterise constipation-driven endophenotypes in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Parkinson Disease and the Gut: A Primer for Gastroenterologists.The American journal of gastroenterology · 2025Review
- Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load.Acta neuropathologica · 2025Article
- Amygdala-predominant Lewy bodies associate with cognitive decline and amygdala atrophy in Alzheimer's disease neuropathological change.Journal of neurology · 2025Article
- MicroRNAs and synaptic dysfunction in Parkinson's disease.Molecular therapy. Nucleic acids · 2025Review
- Hippocampal tau distribution in primary age-related tauopathy: The Vantaa 85+ Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Myocardial sympathetic distal axon loss in subjects with Lewy pathology in three autopsy cohorts.Acta neuropathologica · 2025Article
- The Gut-Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications.Movement disorders clinical practice · 2025Review
- Alzheimer's disease and its co-pathologies: Implications for hippocampal degeneration, cognitive decline, and the role of APOE ε4.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Data-driven characterization of distinct cognitive subtypes in Parkinson's disease dementia.NPJ Parkinson's disease · 2025Article
- Demographic and Clinical Characteristics in Different Motor Subtypes of Parkinson's Disease: How Well Do the Findings Fit Within the Framework of Existing Hypotheses?Neurology international · 2025Article
- Neuropathological stages of neuronal, astrocytic and oligodendrocytic alpha-synuclein pathology in Parkinson's disease.Acta neuropathologica communications · 2025Article
- Early Changes in the Locus Coeruleus in Mild Cognitive Impairment with Lewy Bodies.Movement disorders : official journal of the Movement Disorder Society · 2025Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
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Abstract
According to a generally accepted concept Lewy-related pathology (LRP) follows hierarchical caudo-rostral progression. LRP is also frequently present concomitantly with Alzheimer's disease (AD), and it has been hypothesized that AD-associated LRP forms a distinct type of α-synucleinopathy, where LRP originates in the amygdala. The frequency of distinct forms of LRP progression types has not been studied in a population-based setting. We investigated the distribution and progression of LRP and its relation to AD pathology and apolipoprotein (APOE) ε4 in a population-based sample of Finns aged over 85 years (N = 304). Samples from spinal cord to neocortical areas representing 11 anatomical sites without any hierarchical selection were analyzed immunohistochemically (α-synuclein antibody clone 5G4). LRP was present in 124 individuals (41%) and according to DLB Consortium guidelines 19 of them were categorized as brainstem, 10 amygdala-predominant, 41 limbic, and 43 diffuse neocortical type, whereas 11 could not be classified. To determine the LRP progression patterns, a systematic anatomical scoring was carried out by taking into account the densities of the semiquantitative LRP scores in each anatomic site. With this scoring 123 (99%) subjects could be classified into two progression pattern types: 67% showed caudo-rostral and 32% amygdala-based progression. The unsupervised statistical K-means cluster analysis was used as a supplementary test and supported the presence of two progression patterns and had a 90% overall concordance with the systematic anatomical scoring method. Severe Braak NFT stage, high CERAD score and APOE ε4 were significantly (all p < 0.00001) associated with amygdala-based, but not with caudo-rostral progression type (all p > 0.2). This population-based study demonstrates two distinct common LRP progression patterns in the very elderly population. The amygdala-based pattern was associated with APOE ε4 and AD pathology. The results confirm the previous progression hypotheses but also widen the concept of the AD-associated LRP.
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