An updated review of Parkinson's disease genetics and clinicopathological correlations
Open accessAbstract
Knowledge regarding the pathophysiological basis of Parkinson's disease (PD) has been greatly expanded over the past two decades, with extraordinary contributions from the field of genetics. However, genetic classifications became complex, difficult to follow, and at times misleading, by placing well-established monogenic forms of the disease along with others associated with risk loci, often ill characterized. The present paper summarizes the genetic, clinical, and neuropathological findings of the currently described monogenic forms of PD and also approaches the progress made in determining genetic risk factors for PD. Furthermore, the text incorporates the data into a recently proposed classification system that will hopefully bring a "user-friendly" approach to this issue. This paper also highlights a number of inconsistencies regarding classification of PD as a single, unique clinicopathological entity-in fact, in order to achieve the development of truly innovative therapies, PD should probably be regarded clinically as a "Parkinson's disease cluster", instead of a single disease. In the future, we hope that an in-depth and groundbreaking understanding of PD will allow the development of truly disease-modifying therapies that will target the molecular processes responsible for the cascade of pathological events underlying each form of PD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mutations in PRKN and PINK1 have been identified in familial and sporadic PD.
“Mutations in PRKN (which is encoded by PARK2 gene) and PINK1 (which is encoded by PARK6 gene) have also been identified in familial and sporadic PD.266”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [266]
Cites
MDS clinical diagnostic criteria for Parkinson’s disease
Postuma, R. B., Berg, D., Stern, M., Poewe, W., Olanow, C. W., Oertel, W., Obeso, J., Marek, K., Litvan, I., Lang, A. E., et al. (2015) · Movement Disorders · doi:10.1002/mds.26424 · Cited by 7,653 · see citing works
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in <i>PINK1</i>
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481 · see citing works
International Parkinson's Disease Genomics Consortium (IPDGC), Nalls, M. A., Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Investigator, T. A. J. D., (CHARGE), C. F. H. A. A. R. I. G. E., North American Brain Expression Consortium (NABEC), et al. (2014) · Nature Genetics · doi:10.1038/ng.3043 · Cited by 1,895 · see citing works
Mapping of a gene for Parkinson's disease to chromosome 4q21-q23
Polymeropoulos, M. H., Higgins, J. J., Golbe, L. I., Johnson, W. G., Ide, S. E., Di Iorio, G., Sanges, G., Stenroos, E. S., Pho, L. T., Schaffer, A. A., et al. (1996) · Science · doi:10.1126/science.274.5290.1197 · Cited by 788 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
“A Phase III clinical trial is also undergoing for exenatide, an analogue of GDP-1, as a potential disease-modifying treatment for PD.575 Clinical trials of other drugs including AKST4290, BIIB094, DNL151, DNL201, NE3107 and sargramostim targeting to different immune modulatory pathways have also made some progress (cl…”
BackgroundInfluentialInflammation and immune dysfunction in Parkinson disease
Tansey, M. G., Wallings, R. L., Houser, M. C., Herrick, M. K., Keating, C. E., & Joers, V. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00684-6 · Cited by 1,382 · see citing works
The genetics of Parkinson disease
Deng, H., Wang, P., & Jankovic, J. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2017.12.007 · Cited by 530 · see citing works
Systematic clinical approach for diagnosing upper limb tremor
Wardt, J. V. D., van der Stouwe, A. M. M., Dirkx, M., Elting, J. W. J., Post, B., Tijssen, M. A., & Helmich, R. C. (2020) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-322676 · Cited by 72 · see citing works
- Authors
- Ferreira, M., & Massano, J.
- Affiliations
- Universidade do Porto (PT)
- Corresponding author
- Massano, J.
- Venue
- Acta Neurologica Scandinavica
- Publisher
- Wiley
- Published
- 2016-06-08
- Volume
- 135
- Issue
- 3
- Pages
- 273-284
- ISSN
- 0001-6314 (ISSN-L)
- OpenAlex
- W2414116245
- Cited by
- 167
- References
- 4
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 18 · 2021: 22 · 2020: 25 · 2019: 24 · 2018: 27 · 2017: 15 · 2016: 6
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Neurologica Scandinavica (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Novartis
- Centro de Investigação Clínica, Centro Hospitalar São João, Porto
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- Parkinson's disease, genetic classification, monogenic Parkinson's disease, genetic susceptibility loci, clinicopathological correlation, neuropathology, disease classification, disease-modifying therapy, pathophysiology
- MeSH terms
- Humans, Parkinson Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
