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Cerebral amyloid angiopathy, APP-related

MedGen UID:
414044
Concept ID:
C2751536
Disease or Syndrome
Synonyms: AMYLOIDOSIS, CEREBROARTERIAL, APP-RELATED; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants
 
Gene (location): APP (21q21.3)
 
Monarch Initiative: MONDO:0011583
OMIM®: 605714

Definition

Cerebral amyloid angiopathy, or cerebroarterial amyloidosis, refers to a pathologic process in which amyloid protein progressively deposits in cerebral blood vessel walls with subsequent degenerative vascular changes that usually result in spontaneous cerebral hemorrhage, ischemic lesions, and progressive dementia. APP-related CAA is the most common form of CAA (Revesz et al., 2003, 2009). [from OMIM]

Additional description

From MedlinePlus Genetics
Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).

Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type also have clouding of the lens of the eyes (cataracts) and deafness.

The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.

People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.

The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).

There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause, which determines whether areas of the brain other than blood vessels are affected, and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.

Hereditary cerebral amyloid angiopathy is a condition characterized by an abnormal buildup of protein clumps called amyloid deposits in the blood vessels in the brain, causing vascular disease (angiopathy). People with hereditary cerebral amyloid angiopathy often have progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.  https://medlineplus.gov/genetics/condition/hereditary-cerebral-amyloid-angiopathy

Clinical features

From HPO
Stroke disorder
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Cerebellar hemorrhage
MedGen UID:
488779
Concept ID:
C0149854
Pathologic Function
Hemorrhage into the parenchyma of the cerebellum.
Cerebral ischemia
MedGen UID:
182975
Concept ID:
C0917798
Pathologic Function
Restriction of arterial blood supply to the brain associated with insufficient oxygenation to support the metabolic requirements of the tissue.
Tortuous cerebral arteries
MedGen UID:
373178
Concept ID:
C1836791
Finding
Excessive bending, twisting, and winding of a cerebral artery.
Recurrent cerebral hemorrhage
MedGen UID:
870807
Concept ID:
C4025264
Disease or Syndrome
Recurrent bleeding into the parenchyma of the brain.
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Subarachnoid hemorrhage
MedGen UID:
11625
Concept ID:
C0038525
Disease or Syndrome
Hemorrhage occurring between the arachnoid mater and the pia mater.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Cerebral amyloid angiopathy
MedGen UID:
38998
Concept ID:
C0085220
Disease or Syndrome
Hereditary cerebral amyloid angiopathy is a condition characterized by an abnormal buildup of protein clumps called amyloid deposits in the blood vessels in the brain, causing vascular disease (angiopathy). People with hereditary cerebral amyloid angiopathy often have progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.\n\nThere are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause, which determines whether areas of the brain other than blood vessels are affected, and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.\n\nThe Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).\n\nPeople with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.\n\nThe first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.\n\nTwo types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type also have clouding of the lens of the eyes (cataracts) and deafness.\n\nStrokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCerebral amyloid angiopathy, APP-related

Professional guidelines

PubMed

van Etten ES, Kaushik K, van Zwet EW, Voigt S, van Walderveen MAA, van Buchem MA, Terwindt GM, Wermer MJH
Stroke 2020 Dec;51(12):3608-3612. Epub 2020 Nov 5 doi: 10.1161/STROKEAHA.120.031264. PMID: 33148142

Recent clinical studies

Etiology

Chatterjee P, Fagan AM, Xiong C, McKay M, Bhatnagar A, Wu Y, Singh AK, Taddei K, Martins I, Gardener SL, Molloy MP, Multhaup G, Masters CL, Schofield PR, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, Wermer MJH, van Buchem MA, Sohrabi HR, Martins RN; Dominantly Inherited Alzheimer Network
J Alzheimers Dis 2021;79(2):895-903. doi: 10.3233/JAD-201267. PMID: 33361604Free PMC Article
van Etten ES, Kaushik K, van Zwet EW, Voigt S, van Walderveen MAA, van Buchem MA, Terwindt GM, Wermer MJH
Stroke 2020 Dec;51(12):3608-3612. Epub 2020 Nov 5 doi: 10.1161/STROKEAHA.120.031264. PMID: 33148142
Koemans EA, Voigt S, Rasing I, van Etten ES, van Zwet EW, van Walderveen MAA, Wermer MJH, Terwindt GM
Stroke 2020 Apr;51(4):1094-1099. Epub 2020 Mar 2 doi: 10.1161/STROKEAHA.119.028170. PMID: 32114932
Koemans EA, van Etten ES, van Opstal AM, Labadie G, Terwindt GM, Wermer MJH, Webb AG, Gurol EM, Greenberg SM, van Buchem MA, van der Grond J, van Rooden S
Stroke 2018 Jun;49(6):1518-1520. Epub 2018 Apr 25 doi: 10.1161/STROKEAHA.117.020302. PMID: 29695466Free PMC Article

Diagnosis

Chatterjee P, Fagan AM, Xiong C, McKay M, Bhatnagar A, Wu Y, Singh AK, Taddei K, Martins I, Gardener SL, Molloy MP, Multhaup G, Masters CL, Schofield PR, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, Wermer MJH, van Buchem MA, Sohrabi HR, Martins RN; Dominantly Inherited Alzheimer Network
J Alzheimers Dis 2021;79(2):895-903. doi: 10.3233/JAD-201267. PMID: 33361604Free PMC Article
van Etten ES, Kaushik K, van Zwet EW, Voigt S, van Walderveen MAA, van Buchem MA, Terwindt GM, Wermer MJH
Stroke 2020 Dec;51(12):3608-3612. Epub 2020 Nov 5 doi: 10.1161/STROKEAHA.120.031264. PMID: 33148142
Koemans EA, Voigt S, Rasing I, van Etten ES, van Zwet EW, van Walderveen MAA, Wermer MJH, Terwindt GM
Stroke 2020 Apr;51(4):1094-1099. Epub 2020 Mar 2 doi: 10.1161/STROKEAHA.119.028170. PMID: 32114932
Schouten TM, de Vos F, van Rooden S, Bouts MJRJ, van Opstal AM, Feis RA, Terwindt GM, Wermer MJH, van Buchem MA, Greenberg SM, de Rooij M, Rombouts SARB, van der Grond J
J Am Heart Assoc 2019 Feb 5;8(3):e011288. doi: 10.1161/JAHA.118.011288. PMID: 30717612Free PMC Article

Clinical prediction guides

Koemans EA, Rasing I, Voigt S, van Harten TW, van der Zwet RGJ, Kaushik K, Schipper MR, van der Weerd N, van Zwet EW, van Etten ES, van Osch MJP, Kuiperij B, Verbeek MM, Terwindt GM, Greenberg SM, van Walderveen MAA, Wermer MJH
Stroke 2024 Apr;55(4):954-962. Epub 2024 Mar 6 doi: 10.1161/STROKEAHA.123.044688. PMID: 38445479Free PMC Article
Chatterjee P, Fagan AM, Xiong C, McKay M, Bhatnagar A, Wu Y, Singh AK, Taddei K, Martins I, Gardener SL, Molloy MP, Multhaup G, Masters CL, Schofield PR, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, Wermer MJH, van Buchem MA, Sohrabi HR, Martins RN; Dominantly Inherited Alzheimer Network
J Alzheimers Dis 2021;79(2):895-903. doi: 10.3233/JAD-201267. PMID: 33361604Free PMC Article
Grand Moursel L, van der Graaf LM, Bulk M, van Roon-Mom WMC, van der Weerd L
Brain Pathol 2019 Nov;29(6):793-802. Epub 2019 Apr 4 doi: 10.1111/bpa.12721. PMID: 30868685Free PMC Article
Bulk M, Moursel LG, van der Graaf LM, van Veluw SJ, Greenberg SM, van Duinen SG, van Buchem MA, van Rooden S, van der Weerd L
Stroke 2018 Sep;49(9):2081-2087. doi: 10.1161/STROKEAHA.118.021872. PMID: 30354978
Koemans EA, van Etten ES, van Opstal AM, Labadie G, Terwindt GM, Wermer MJH, Webb AG, Gurol EM, Greenberg SM, van Buchem MA, van der Grond J, van Rooden S
Stroke 2018 Jun;49(6):1518-1520. Epub 2018 Apr 25 doi: 10.1161/STROKEAHA.117.020302. PMID: 29695466Free PMC Article

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