Pathophysiology of non-Alzheimer dementias: synucleinopathies, frontotemporal lobar degeneration and vascular injury
Dementia as a set of protein misfolding and vascular disorders. Alpha-synuclein in Lewy body disease and MSA (with the biology behind RBD, neuroleptic sensitivity, DaT and MIBG imaging and seed amplification assays), tau, TDP-43 and FUS in frontotemporal lobar degeneration with C9orf72, GRN and MAPT, small vessel and strategic vascular injury including CADASIL, LATE and prion disease.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Most dementia is caused by misfolded proteins that aggregate and spread through connected networks, or by vascular injury to white matter and strategic grey matter. The protein and its location determine the syndrome.
- Synucleinopathies: alpha-synuclein in neurons (Parkinson disease dementia, dementia with Lewy bodies) or in oligodendrocytes (multiple system atrophy).
- Frontotemporal lobar degeneration (FTLD): tau, TDP-43 or FUS in frontal and anterior temporal lobes.
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Sources
- McKeith IG et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 2017;89:88-100Neurology, 2017
- Rascovsky K et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011;134:2456-77Brain (Oxford University Press), 2011
- Mackenzie IRA, Neumann M. Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. J Neurochem 2016;138 Suppl 1:54-70Journal of Neurochemistry, 2016
- Nelson PT et al. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain 2019;142:1503-27Brain (Oxford University Press), 2019
- Wardlaw JM et al. Small vessel disease: mechanisms and clinical implications. Lancet Neurol 2019;18:684-96The Lancet Neurology, 2019
- Robbins and Cotran Pathologic Basis of Disease (10th ed.)Elsevier (Kumar, Abbas and Aster, 2020), 2020
- Last updated
- 14 November 2026
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