Tags

Type your tag names separated by a space and hit enter

Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85.
Acta Neuropathol. 2019 11; 138(5):771-782.AN

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.

Links

PMC Free PDF

Authors+Show Affiliations

Raunio A
Department of Pathology, HUSLAB, Helsinki University Hospital, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland.
Kaivola K
Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland. Department of Neurology, Helsinki University Hospital, P.O. Box 63, 00014, Helsinki, Finland.
Tuimala J
Department of Pathology, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland.
Kero M
Department of Pathology, HUSLAB, Helsinki University Hospital, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland.
Oinas M
Department of Pathology, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland. Department of Neurosurgery, Helsinki University Hospital, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland.
Polvikoski T
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Paetau A
Department of Pathology, HUSLAB, Helsinki University Hospital, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland.
Tienari PJ
Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland. Department of Neurology, Helsinki University Hospital, P.O. Box 63, 00014, Helsinki, Finland.
Myllykangas L
Department of Pathology, HUSLAB, Helsinki University Hospital, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland. liisa.myllykangas@helsinki.fi.

MeSH

Aged, 80 and overAlzheimer DiseaseBrainDisease ProgressionFemaleHumansLewy BodiesLewy Body DiseaseMaleParkinson Disease

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31494694

Citation

Raunio, Anna, et al. "Lewy-related Pathology Exhibits Two Anatomically and Genetically Distinct Progression Patterns: a Population-based Study of Finns Aged 85." Acta Neuropathologica, vol. 138, no. 5, 2019, pp. 771-782.
Raunio A, Kaivola K, Tuimala J, et al. Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85. Acta Neuropathol. 2019;138(5):771-782.
Raunio, A., Kaivola, K., Tuimala, J., Kero, M., Oinas, M., Polvikoski, T., Paetau, A., Tienari, P. J., & Myllykangas, L. (2019). Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85. Acta Neuropathologica, 138(5), 771-782. https://doi.org/10.1007/s00401-019-02071-3
Raunio A, et al. Lewy-related Pathology Exhibits Two Anatomically and Genetically Distinct Progression Patterns: a Population-based Study of Finns Aged 85. Acta Neuropathol. 2019;138(5):771-782. PubMed PMID: 31494694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85. AU - Raunio,Anna, AU - Kaivola,Karri, AU - Tuimala,Jarno, AU - Kero,Mia, AU - Oinas,Minna, AU - Polvikoski,Tuomo, AU - Paetau,Anders, AU - Tienari,Pentti J, AU - Myllykangas,Liisa, Y1 - 2019/09/07/ PY - 2019/06/26/received PY - 2019/08/30/accepted PY - 2019/08/17/revised PY - 2019/9/9/pubmed PY - 2020/9/17/medline PY - 2019/9/9/entrez KW - Aged, 80 and over KW - Alzheimer’s disease KW - Lewy body diseases KW - Lewy-related pathology KW - Population-based KW - α-Synuclein SP - 771 EP - 782 JF - Acta neuropathologica JO - Acta Neuropathol VL - 138 IS - 5 N2 - 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. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/31494694/Lewy_related_pathology_exhibits_two_anatomically_and_genetically_distinct_progression_patterns:_a_population_based_study_of_Finns_aged_85_ DB - PRIME DP - Unbound Medicine ER -