Clinical Considerations in Early-onset Cerebral Amyloid Angiopathy

Overview

Journal Brain

Publisher Oxford University Press

Specialty Neurology

Date 2023 Jun 6

PMID 37280119

Authors

Gargi Banerjee

John Collinge

Nick C Fox

Tammaryn Lashley

Simon Mead

Jonathan M Schott

David J Werring

Natalie S Ryan

Affiliations

Soon will be listed here.

Abstract

Cerebral amyloid angiopathy (CAA) is an important cerebral small vessel disease associated with brain haemorrhage and cognitive change. The commonest form, sporadic amyloid-β CAA, usually affects people in mid- to later life. However, early-onset forms, though uncommon, are increasingly recognized and may result from genetic or iatrogenic causes that warrant specific and focused investigation and management. In this review, we firstly describe the causes of early-onset CAA, including monogenic causes of amyloid-β CAA (APP missense mutations and copy number variants; mutations of PSEN1 and PSEN2) and non-amyloid-β CAA (associated with ITM2B, CST3, GSN, PRNP and TTR mutations), and other unusual sporadic and acquired causes including the newly-recognized iatrogenic subtype. We then provide a structured approach for investigating early-onset CAA, and highlight important management considerations. Improving awareness of these unusual forms of CAA amongst healthcare professionals is essential for facilitating their prompt diagnosis, and an understanding of their underlying pathophysiology may have implications for more common, late-onset, forms of the disease.

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References

. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial. Lancet Neurol. 2021; 20(10):842-853. DOI: 10.1016/S1474-4422(21)00264-7. View

Cabral-Macias J, Garcia-Montano L, Perezpena-Diazconti M, Aguilar M, Garcia G, Vencedor-Meraz C . Clinical, histopathological, and in silico pathogenicity analyses in a pedigree with familial amyloidosis of the Finnish type (Meretoja syndrome) caused by a novel gelsolin mutation. Mol Vis. 2020; 26:345-354. PMC: 7195602. View

Raposo N, Planton M, Siegfried A, Calviere L, Payoux P, Albucher J . Amyloid-β transmission through cardiac surgery using cadaveric dura mater patch. J Neurol Neurosurg Psychiatry. 2020; 91(4):440-441. DOI: 10.1136/jnnp-2019-321927. View

van Etten E, Kaushik K, van Zwet E, Voigt S, van Walderveen M, van Buchem M . Sensitivity of the Edinburgh Criteria for Lobar Intracerebral Hemorrhage in Hereditary Cerebral Amyloid Angiopathy. Stroke. 2020; 51(12):3608-3612. DOI: 10.1161/STROKEAHA.120.031264. View

Ye X, Li G, Liu X, Song G, Jia Y, Wu C . Apolipoprotein E genotype predicts subarachnoid extension in spontaneous intracerebral haemorrhage. Eur J Neurol. 2021; 28(6):1992-1999. DOI: 10.1111/ene.14830. View

Sanchez-Caro J, de Lorenzo Martinez de Ubago I, de Celis Ruiz E, Arribas A, Calviere L, Raposo N . Transient Focal Neurological Events in Cerebral Amyloid Angiopathy and the Long-term Risk of Intracerebral Hemorrhage and Death: A Systematic Review and Meta-analysis. JAMA Neurol. 2021; 79(1):38-47. PMC: 8593834. DOI: 10.1001/jamaneurol.2021.3989. View

Grangeon L, Cassinari K, Rousseau S, Croisile B, Formaglio M, Moreaud O . Early-Onset Cerebral Amyloid Angiopathy and Alzheimer Disease Related to an APP Locus Triplication. Neurol Genet. 2021; 7(5):e609. PMC: 8439959. DOI: 10.1212/NXG.0000000000000609. View

Kalampokini S, Georgouli D, Patrikiou E, Provatas A, Valotassiou V, Georgoulias P . Τhe Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations. Int J Mol Sci. 2021; 22(22). PMC: 8622139. DOI: 10.3390/ijms222212355. View

Psychogios K, Xiromerisiou G, Kargiotis O, Safouris A, Fiolaki A, Bonakis A . Hereditary cerebral amyloid angiopathy mimicking CADASIL syndrome. Eur J Neurol. 2021; 28(11):3866-3869. DOI: 10.1111/ene.14981. View

10.

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

11.

Fanou E, Coutinho J, Shannon P, Kiehl T, Levi M, Wilcox M . Critical Illness-Associated Cerebral Microbleeds. Stroke. 2017; 48(4):1085-1087. DOI: 10.1161/STROKEAHA.116.016289. View

12.

Greenberg S, Briggs M, Hyman B, Kokoris G, Takis C, Kanter D . Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke. 1996; 27(8):1333-7. DOI: 10.1161/01.str.27.8.1333. View

13.

Nicolas G, Wallon D, Goupil C, Richard A, Pottier C, Dorval V . Mutation in the 3'untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy. Eur J Hum Genet. 2015; 24(1):92-8. PMC: 4795229. DOI: 10.1038/ejhg.2015.61. View

14.

Revesz T, Holton J, Lashley T, Plant G, Frangione B, Rostagno A . Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009; 118(1):115-30. PMC: 2844092. DOI: 10.1007/s00401-009-0501-8. View

15.

Murrell J, Farlow M, Ghetti B, Benson M . A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science. 1991; 254(5028):97-9. DOI: 10.1126/science.1925564. View

16.

Ziff O, Banerjee G, Ambler G, Werring D . Statins and the risk of intracerebral haemorrhage in patients with stroke: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2018; 90(1):75-83. DOI: 10.1136/jnnp-2018-318483. View

17.

Thal D, Ghebremedhin E, Rub U, Yamaguchi H, Del Tredici K, Braak H . Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002; 61(3):282-93. DOI: 10.1093/jnen/61.3.282. View

18.

Selkoe D, Wolfe M . Presenilin: running with scissors in the membrane. Cell. 2007; 131(2):215-21. DOI: 10.1016/j.cell.2007.10.012. View

19.

Garzuly F, Vidal R, Wisniewski T, Brittig F, Budka H . Familial meningocerebrovascular amyloidosis, Hungarian type, with mutant transthyretin (TTR Asp18Gly). Neurology. 1996; 47(6):1562-7. DOI: 10.1212/wnl.47.6.1562. View

20.

Wardlaw J, Smith E, Biessels G, Cordonnier C, Fazekas F, Frayne R . Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013; 12(8):822-38. PMC: 3714437. DOI: 10.1016/S1474-4422(13)70124-8. View