Iatrogenic cerebral proteinopathies—The dawn of transmissible neurodegeneration? The example of cerebral amyloid angiopathy

Topic: Brain proteins, microglia and lab models

Several reports confirmed possible inadvertent iatrogenic intracranial transmission of Aβ pathology via medical and surgical procedures (1,2).A common molecular mechanism, described in prion diseases, is proposed to trigger the replication and spread of different misfolded proteins in the central nervous system (CNS), causing different neurodegenerative diseases associated with disease-specific proteins such as α-synuclein in Parkinson's disease, and amyloid-beta (Aβ) in Alzheimer's disease, and cerebral amyloid angiopathy (CAA) (3). Medical procedures involving exposure to Aβ beyond childhood have been associated with possible iCAA in elderly patients (19). The growing literature on iCAA raises critical, medico-legal, and ethical questions-particularly regarding organ and tissue donor programs-and disclosure of diagnosis in clinical practice due to uncertainty about iCAA etiology, prognosis, and lack of treatments.This opinion argues for an increased clinical, medico-legal, and ethical awareness of iCAA in younger patients presenting with atypical ICH.Growing literature suggests that misfolded proteins, specifically Aβ, can be transmitted from person to person in a prion-like propagation through various medical and neurosurgical procedures. The appearance of Aβ seeding in the cerebral blood vessels a few decades after neurosurgical interventions indicates probable vascular complications associated with iCAA, including ICH, perivascular inflammation, and cognitive impairment (2).Disclosing the possibility of iCAA to a patient with symptoms compatible with CAA and a history of relevant exposure to exogenous Aβ conforms to the informed consent principle and is a prerequisite for respecting the patient's autonomy (23). In iCAA, it opens up relevant ethical considerations since this diagnosis is often associated with a certain uncertainty (20).

@article{zupan2025-41281549,
  author  = {Zupan, Matija and Splavski, Bruno and Frol, Senta},
  title   = {{Iatrogenic cerebral proteinopathies—The dawn of transmissible neurodegeneration? The example of cerebral amyloid angiopathy}},
  journal = {Frontiers in Neurology},
  year    = {2025},
  doi     = {10.3389/fneur.2025.1693566},
  pmid    = {41281549},
  url     = {https://doi.org/10.3389/fneur.2025.1693566}
}

Key findings

• Several reports confirmed possible inadvertent iatrogenic intracranial transmission of Aβ pathology via medical and surgical procedures (1,2).A common molecular mechanism, described in prion diseases, is proposed to trigger the replication and spread of different misfolded proteins in the central nervous system (CNS), causing different neurodegenerative diseases associated with disease-specific proteins such as α-synuclein in Parkinson's disease, and amyloid-beta (Aβ) in Alzheimer's disease, and cerebral amyloid angiopathy (CAA) (3).
• Medical procedures involving exposure to Aβ beyond childhood have been associated with possible iCAA in elderly patients (19).
• The growing literature on iCAA raises critical, medico-legal, and ethical questions-particularly regarding organ and tissue donor programs-and disclosure of diagnosis in clinical practice due to uncertainty about iCAA etiology, prognosis, and lack of treatments.This opinion argues for an increased clinical, medico-legal, and ethical awareness of iCAA in younger patients presenting with atypical ICH.Growing literature suggests that misfolded proteins, specifically Aβ, can be transmitted from person to person in a prion-like propagation through various medical and neurosurgical procedures.
• The appearance of Aβ seeding in the cerebral blood vessels a few decades after neurosurgical interventions indicates probable vascular complications associated with iCAA, including ICH, perivascular inflammation, and cognitive impairment (2).Disclosing the possibility of iCAA to a patient with symptoms compatible with CAA and a history of relevant exposure to exogenous Aβ conforms to the informed consent principle and is a prerequisite for respecting the patient's autonomy (23).
• In iCAA, it opens up relevant ethical considerations since this diagnosis is often associated with a certain uncertainty (20).

Why it matters

This opinion piece discusses reports that misfolded amyloid-beta can be transmitted between people through certain medical and surgical procedures, in a prion-like way, potentially causing cerebral amyloid angiopathy decades later. It argues for greater clinical, legal, and ethical awareness of this possibility, especially in younger patients with atypical brain hemorrhage.

Study details

• Participants125
• Evidence strengthLow

Read the original

• DOI: 10.3389/fneur.2025.1693566
• PubMed: 41281549
• Original source →
• Free full text: Frontiers in Neurology →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Related

Studies in the library that share something with this one. The line above each title says what.

• same condition: cerebral amyloid angiopathy; same population: older adults Cerebral amyloid angiopathy in the elderly Annals of neurology · 2011-12-01 · usefulness score 55/100
• same condition: cerebral amyloid angiopathy; same population: older adults The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage Neurology · 1993-10-01 · usefulness score 52/100
• same condition: cerebral amyloid angiopathy; same population: older adults Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline Journal of neuropathology and experimental neurology · 2003-12-01 · usefulness score 45/100
• same condition: cerebral amyloid angiopathy; same population: older adults Identifying potential drug targets for cerebral amyloid angiopathy: A Mendelian randomization study based on the druggable genes Medicine · 2025-10-31 · usefulness score 33/100
• same condition: cerebral amyloid angiopathy; same population: older adults Cortical Gray Matter Proteins Associated With Cerebral Amyloid Angiopathy in Community-Dwelling Older Adults Neurology · 2025-08-22 · usefulness score 50/100
• same condition: cerebral amyloid angiopathy; same population: older adults Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy Neurology · 2006-01-01 · usefulness score 62/100

Related studies in Brain tissue and pathology

• Cerebrospinal Fluid β‐Amyloid and τ Levels in Patients With Iatrogenic Cerebral Amyloid Angiopathy, Sporadic Cerebral Amyloid Angiopathy, Alzheimer Disease, and Controls Journal of the American Heart Association · 2025-07-29 · usefulness score 49/100
• To reveal and acknowledge an iatrogenic cerebral amyloid angiopathy: a vascular neurologist and neurosurgeon collaborative perspective Frontiers in Neurology · 2025-06-13 · usefulness score 36/100
• Traumatic Brain Injury and Chronic Traumatic Encephalopathy: Not Only Trigger for Neurodegeneration but Also for Cerebral Amyloid Angiopathy? Biomedicines · 2025-04-05 · usefulness score 40/100
• TDP ‐43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models FEBS Journal · 2025-09-02 · usefulness score 43/100
• Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons Neurology · 2015-11-04 · usefulness score 70/100
• Cerebral amyloid angiopathy pathology and cognitive domains in older persons Annals of neurology · 2010-11-08 · usefulness score 68/100

Also tagged “precursor”

1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.

• Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: a meta-analysis Journal of neurology, neurosurgery, and psychiatry · 2011-04-14 · usefulness score 67/100 · Mild cognitive impairment
• Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease Archives of neurology · 2007-03-01 · usefulness score 57/100 · How common it is
• Neuroanatomical spread of amyloid β and tau in Alzheimer's disease: implications for primary prevention Brain communications · 2020-02-06 · usefulness score 65/100 · Mild cognitive impairment

Studies sharing this one's topic tags

• APOE4 homozygosity represents a distinct genetic form of Alzheimer's disease Nature Medicine · 2024-05 · usefulness score 61/100 · shares: precursor, apoe
• APOE2 is associated with longevity independent of Alzheimer's disease eLife · 2020-10-19 · usefulness score 65/100 · shares: precursor, apoe
• Retraction Note: A specific amyloid-beta protein assembly in the brain impairs memory Nature · 2024-06-24 · usefulness score 16/100 · shares: precursor, apoe
• NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice Nature · 2012-12-19 · usefulness score 62/100 · shares: precursor, apoe
• Impact of learning APOE genotype on cognitively unimpaired adults: a pre-screening cohort study of the Alzheimer's Prevention Initiative Generation Study 1 The Lancet Healthy Longevity · 2025-11-27 · usefulness score 63/100 · shares: precursor, apoe

Similar studies

• Cerebral amyloid angiopathy: emerging concepts 2015 · Getting a diagnosis
• Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view 2003 · Brain tissue and pathology
• Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain 2003 · Risk genes beyond APOE
• Two types of sporadic cerebral amyloid angiopathy 2002 · Genetics
• Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways 2020 · Brain tissue and pathology
• A plasma protein signature for cerebral amyloid angiopathy 2026 · Treatments

More on Brain tissue and pathology

• A review that covers this ground Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions Brain : a journal of neurology · 2015-06-26 · usefulness score 56/100
• Newest in this subject Inflammatory biomarker candidates in dementia with Lewy bodies: diagnostic classification, clinical associations, and survival Research Square · 2026-11-01 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject TMEM106B C-Terminal fragment aggregation exacerbates α-synuclein and TDP-43 proteinopathy phenotypes bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Brain tissue and pathology →