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Updated: Dec 7, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
"A case report: Co-occurrence of cerebral amyloid angiopathy and multiple sclerosis"
Dominik Kobylarek1, Piotr Iwanowski1, David Masolak1
1Department of Neurology, Poznan University of Medical Sciences, ul. Przybyszewskiego 49, Poznan, Poland.
Insights
Hereditary cerebral amyloid angiopathy (CAA) with an APP gene mutation was diagnosed in a patient with multiple sclerosis (MS). This case highlights a potential link between amyloid accumulation and MS progression, suggesting amyloid-PET may aid in diagnosing MS-related demyelination.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Cerebral amyloid angiopathy (CAA) involves amyloid protein buildup in brain blood vessels, potentially causing hemorrhage, ischemic injury, and cognitive decline.
- Hereditary forms of CAA, such as the Iowa-type mutation in the APP gene, follow an autosomal dominant inheritance pattern.
- Multiple Sclerosis (MS) is a chronic neurological disease affecting the central nervous system.
Observation:
- A patient with a familial history of intracerebral hemorrhage was diagnosed with the Iowa-type hereditary CAA mutation (APP D694N).
- This patient also presented with a diagnosis of multiple sclerosis (MS) according to McDonald criteria.
- The APP gene mutation was identified in other family members, consistent with autosomal dominant inheritance.
Findings:
- The coexistence of hereditary cerebral amyloid angiopathy (CAA) with an APP gene mutation and multiple sclerosis (MS) in the same patient is reported.
- Amyloid accumulation in the central nervous system (CNS) is increasingly linked to MS pathogenesis and progression.
- Amyloid positron-emission tomography (amyloid-PET) shows potential as a diagnostic tool for assessing demyelination and remyelination in MS.
Implications:
- This case suggests a potential role for amyloid in neuroimmunology and MS pathogenesis.
- Accumulation of amyloid precursor protein (APP) in the CNS may serve as a biomarker for MS progression.
- Amyloid-PET imaging could offer new insights into the pathological processes and disease activity in multiple sclerosis.
Abstract:
Cerebral amyloid angiopathy (CAA) is a chronic pathological condition characterized by progressive accumulation of amyloid protein in the wall of cerebral blood vessels, both leptomeningeal and cortical. That may result in the development of such conditions as microaneurysms, hemorrhagic, ischaemic brain injury and contribute to cognitive impairment. We herein report a case of Iowa-type hereditary cerebral amyloid angiopathy (CAA) mutation diagnosed with MS. The family of the reported patient had performed genetic testing due to the history of intracerebral hemorrhage. Sequence analysis of exon 17 of the APP gene showed the presence of the D694N g.275272 G > A (c.2080 G > A) mutation, which caused the substitution of aspartate for aspargine at position 694 of APP. Alike the discussed patient, this mutation has been found in other family members in an autosomal dominant pattern of inheritance. Contrary to the rest of the family, the reported patient has been diagnosed with multiple sclerosis based on McDonald criteria. Recent studies shed light on the possible link between the APP accumulation and MS progression. It has been indicated that amyloid can prove a vital role in neuroimmunology, whereas the accumulation of APP in the CNS has been suggested to be a potential biomarker for the progression of MS. Moreover, the amyloid positron-emission tomography (amyloid-PET) has been demonstrated to serve as a diagnostic tool for establishing the degree of demyelination and remyelination in MS. Even though, one swallow does not make a summer, this finding would be another step forward in the understanding of pathological processes underlying the pathogenesis of MS.
