CAA-APP
MCID: CRB193
MIFTS: 45

Cerebral Amyloid Angiopathy, App-Related (CAA-APP)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Cerebral Amyloid Angiopathy, App-Related

MalaCards integrated aliases for Cerebral Amyloid Angiopathy, App-Related:

Name: Cerebral Amyloid Angiopathy, App-Related 58 76 30 6 41
Hchwad 58 12 76
Cerebral Amyloid Angiopathy, Dutch, Italian, Iowa, Flemish, Arctic Variants 58 13
Amyloidosis, Hereditary, with Cerebral Hemorrhage, Dutch Variant 58 12
Cerebral Amyloid Angiopathy, App-Related, Italian Variant 58 12
Cerebral Amyloid Angiopathy, App-Related, Flemish Variant 58 12
Cerebral Amyloid Angiopathy, App-Related, Arctic Variant 58 12
Cerebral Amyloid Angiopathy, App-Related, Dutch Variant 58 12
Cerebral Amyloid Angiopathy, App-Related, Iowa Variant 58 12
Amyloidosis, Cerebroarterial, App-Related 58 12
App-Related Cerebral Amyloid Angiopathy 12 15
Hchwa-D 60 76
Familial Occipital Calcifications with Hemorrhagic Strokes Leukoencephalopathy Arterial Dysplasia Dementia 76
Amyloidosis, Hereditary, with Cerebral Hemorrhage, Dutch Variant; Hchwad 58
Hereditary Cerebral Hemorrhage with Amyloidosis, Piedmont Type 60
Hereditary Cerebral Hemorrhage with Amyloidosis, Flemish Type 60
Hereditary Cerebral Hemorrhage with Amyloidosis, Italian Type 60
Amyloidosis Hereditary with Cerebral Hemorrhage Dutch Variant 76
Hereditary Cerebral Hemorrhage with Amyloidosis, Arctic Type 60
Hereditary Cerebral Hemorrhage with Amyloidosis Italian Type 76
Cerebral Hemorrhage with Amyloidosis, Hereditary, Dutch Type 74
Hereditary Cerebral Hemorrhage with Amyloidosis, Dutch Type 60
Hereditary Cerebral Hemorrhage with Amyloidosis, Iowa Type 60
Hereditary Cerebral Hemorrhage with Amyloidosis Dutch Type 76
Cerebral Amyloid Angiopathy App-Related Flemish Variant 76
Cerebral Amyloid Angiopathy App-Related Italian Variant 76
Cerebral Amyloid Angiopathy App-Related Arctic Variant 76
Cerebral Amyloid Angiopathy App-Related Dutch Variant 76
Cerebral Amyloid Angiopathy App-Related Iowa Variant 76
Hereditary Cerebral Amyloid Angiopathy Dutch Type 76
Amyloidosis Cerebroarterial App-Related 76
Abeta Amyloidosis, Piedmont Type 60
Abeta Amyloidosis, Flemish Type 60
Abeta Amyloidosis, Italian Type 60
Abeta Amyloidosis, Arctic Type 60
Abetaa21g-Related Amyloidosis 60
Abetal34v-Related Amyloidosis 60
Abeta Amyloidosis, Dutch Type 60
Abeta Amyloidosis, Iowa Type 60
Abetaa21g Amyloidosis 60
Abetae22k Amyloidosis 60
Abetae22g Amyloidosis 60
Abetad23n Amyloidosis 60
Abetal34v Amyloidosis 60
Abetae22q Amyloidosis 60
Hchwa, Piedmont Type 60
Hchwa, Flemish Type 60
Hchwa, Italian Type 60
Hchwa, Arctic Type 60
Hchwa, Dutch Type 60
Hchwa, Iowa Type 60
Fochs-Ladd 76
Caa-App 76

Characteristics:

Orphanet epidemiological data:

60
abetaa21g amyloidosis
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult; Age of death: adult;
abeta amyloidosis, italian type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult,Elderly; Age of death: adult,elderly;
abeta amyloidosis, arctic type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult,Elderly;
abeta amyloidosis, iowa type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Elderly; Age of death: elderly;
abetal34v amyloidosis
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult,Elderly; Age of death: elderly;
abeta amyloidosis, dutch type
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult; Age of death: adult;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
onset in middle age (44 to 60 years)
allelic to early-onset familial alzheimer disease (ad1, )


HPO:

33
cerebral amyloid angiopathy, app-related:
Mortality/Aging death in early adulthood
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Cerebral Amyloid Angiopathy, App-Related

UniProtKB/Swiss-Prot : 76 Cerebral amyloid angiopathy, APP-related: A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.

MalaCards based summary : Cerebral Amyloid Angiopathy, App-Related, also known as hchwad, is related to cerebral hemorrhage and amyloidosis. An important gene associated with Cerebral Amyloid Angiopathy, App-Related is APP (Amyloid Beta Precursor Protein), and among its related pathways/superpathways is A-beta Pathways: Plaque Formation and APP Metabolism. Affiliated tissues include brain, bone and cerebellum, and related phenotypes are intellectual disability and gait disturbance

Disease Ontology : 12 A cerebral amyloid angiopathy that has material basis in an autosomal dominant mutation of APP on chromosome 21q21.3.

OMIM : 58 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 (25,26:Revesz et al., 2003, 2009). (605714)

Related Diseases for Cerebral Amyloid Angiopathy, App-Related

Graphical network of the top 20 diseases related to Cerebral Amyloid Angiopathy, App-Related:



Diseases related to Cerebral Amyloid Angiopathy, App-Related

Symptoms & Phenotypes for Cerebral Amyloid Angiopathy, App-Related

Human phenotypes related to Cerebral Amyloid Angiopathy, App-Related:

60 33 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001249
2 gait disturbance 60 33 hallmark (90%) Very frequent (99-80%) HP:0001288
3 dysphagia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002015
4 behavioral abnormality 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Frequent (79-30%),Very frequent (99-80%) HP:0000708
5 global developmental delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001263
6 myoclonus 60 33 hallmark (90%) Very frequent (99-80%) HP:0001336
7 migraine 60 33 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0002076
8 memory impairment 60 33 hallmark (90%) Very frequent (99-80%) HP:0002354
9 paresthesia 60 33 hallmark (90%) Very frequent (99-80%) HP:0003401
10 febrile seizures 60 33 hallmark (90%) Very frequent (99-80%) HP:0002373
11 dementia 60 33 hallmark (90%) Frequent (79-30%),Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%) HP:0000726
12 coma 60 33 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0001259
13 stroke 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%) HP:0001297
14 headache 60 33 hallmark (90%) Very frequent (99-80%) HP:0002315
15 cerebral hemorrhage 60 33 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%) HP:0001342
16 sensory impairment 60 33 hallmark (90%) Very frequent (99-80%) HP:0003474
17 seizures 60 33 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001250
18 cerebral calcification 60 33 frequent (33%) Frequent (79-30%) HP:0002514
19 cerebral amyloid angiopathy 60 33 frequent (33%) Frequent (79-30%) HP:0011970
20 cerebral ischemia 33 HP:0002637
21 death in early adulthood 60 Occasional (29-5%)
22 abnormality of the cerebral vasculature 60 Very frequent (99-80%),Frequent (79-30%)
23 mental deterioration 60 Frequent (79-30%),Very frequent (99-80%)
24 cerebellar hemorrhage 33 HP:0011695
25 recurrent cerebral hemorrhage 33 HP:0004968
26 tortuous cerebral arteries 33 HP:0004938

Symptoms via clinical synopsis from OMIM:

58
Cardiovascular Vascular:
cerebral ischemia
cerebral amyloid angiopathy
cerebral artery amyloidosis (amyloid deposition in cerebral arteries)
recurrent strokes
cerebral infarction
more
Neurologic Central Nervous System:
dementia, progressive, with onset of disease

Clinical features from OMIM:

605714

Drugs & Therapeutics for Cerebral Amyloid Angiopathy, App-Related

Search Clinical Trials , NIH Clinical Center for Cerebral Amyloid Angiopathy, App-Related

Genetic Tests for Cerebral Amyloid Angiopathy, App-Related

Genetic tests related to Cerebral Amyloid Angiopathy, App-Related:

# Genetic test Affiliating Genes
1 Cerebral Amyloid Angiopathy, App-Related 30 APP

Anatomical Context for Cerebral Amyloid Angiopathy, App-Related

MalaCards organs/tissues related to Cerebral Amyloid Angiopathy, App-Related:

42
Brain, Bone, Cerebellum, Thalamus

Publications for Cerebral Amyloid Angiopathy, App-Related

Articles related to Cerebral Amyloid Angiopathy, App-Related:

(show all 37)
# Title Authors Year
1
Brain Transcriptomic Analysis of Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch Type. ( 29706885 )
2018
2
TGFI^ pathway deregulation and abnormal phospho-SMAD2/3 staining in hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 28557134 )
2017
3
Amyloid I^ in hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 24870607 )
2014
4
Extracellular matrix modulator lysyl oxidase colocalizes with amyloid-beta pathology in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis--Dutch type. ( 23267843 )
2013
5
Small heat shock proteins associated with cerebral amyloid angiopathy of hereditary cerebral hemorrhage with amyloidosis (Dutch type) induce interleukin-6 secretion. ( 17629591 )
2009
6
Cerebral vascular accumulation of Dutch-type Abeta42, but not wild-type Abeta42, in hereditary cerebral hemorrhage with amyloidosis, Dutch type. ( 17628026 )
2007
7
Hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 16382777 )
2005
8
Microbleeds in hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 15824369 )
2005
9
Glial reactions and the clearance of amyloid beta protein in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 15014955 )
2004
10
Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): decreased plasma amyloid-beta 42 concentration. ( 14678776 )
2003
11
Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles. ( 11761474 )
2001
12
Amyloid beta protein (Abeta) starts to deposit as plasma membrane-bound form in diffuse plaques of brains from hereditary cerebral hemorrhage with amyloidosis-Dutch type, Alzheimer disease and nondemented aged subjects. ( 10952062 )
2000
13
Ultrastructural evidence of early non-fibrillar Abeta42 in the capillary basement membrane of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type. ( 10603032 )
1999
14
Hereditary cerebral hemorrhage with amyloidosis--Dutch type (HCHWA-D): a review of the variety in phenotypic expression. ( 10524288 )
1999
15
Secondary microvascular degeneration in amyloid angiopathy of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). ( 9542588 )
1998
16
Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type. ( 9707198 )
1998
17
Presenilin-1 polymorphism and hereditary cerebral hemorrhage with amyloidosis, Dutch type. ( 9225691 )
1997
18
The length of amyloid-beta in hereditary cerebral hemorrhage with amyloidosis, Dutch type. Implications for the role of amyloid-beta 1-42 in Alzheimer's disease. ( 8943274 )
1996
19
Hereditary cerebral hemorrhage with amyloidosis-Dutch type: better correlation of cognitive deterioration with advancing age than with number of focal lesions or white matter hyperintensities. ( 8939282 )
1996
20
Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I--A review of clinical, radiologic and genetic aspects. ( 8737926 )
1996
21
Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): II--A review of histopathological aspects. ( 8737927 )
1996
22
Ubiquitinated neurites are associated with preamyloid and cerebral amyloid beta deposits in patients with hereditary cerebral hemorrhage with amyloidosis Dutch type. ( 8384771 )
1993
23
Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease. ( 7684195 )
1993
24
Hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 8240526 )
1993
25
Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type share a decrease in cerebrospinal fluid levels of amyloid beta-protein precursor. ( 1510361 )
1992
26
Acute phase proteins but not activated microglial cells are present in parenchymal beta/A4 deposits in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 1380141 )
1992
27
Hereditary cerebral hemorrhage with amyloidosis-Dutch type: a study of fibrinolysis. ( 1615471 )
1992
28
Hereditary cerebral hemorrhage with amyloidosis--Dutch type: a congophilic angiopathy. An overview. ( 1776734 )
1991
29
DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type) ( 1679289 )
1991
30
Hereditary cerebral hemorrhage with amyloidosis--Dutch type: its importance for Alzheimer research. ( 1716015 )
1991
31
Alzheimer A4 peptide, gamma-trace, leukoencephalopathy, and hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 2042952 )
1991
32
Parenchymal preamyloid and amyloid deposits in the brains of patients with hereditary cerebral hemorrhage with amyloidosis--Dutch type. ( 2274275 )
1990
33
Hereditary cerebral hemorrhage with amyloidosis--Dutch type. Tc-99m HM-PAO single photon emission computed tomography. ( 2398939 )
1990
34
Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 2396937 )
1990
35
Hereditary cerebral hemorrhage with amyloidosis-Dutch type. Clinical and computed tomographic analysis of 24 cases. ( 2346393 )
1990
36
Hereditary cerebral hemorrhage with amyloidosis--Dutch type. Research-Group Hereditary Cerebral Amyloid-Angiopathy. ( 2555088 )
1989
37
Different processing of Alzheimer's beta-protein precursor in the vessel wall of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type. ( 3281669 )
1988

Variations for Cerebral Amyloid Angiopathy, App-Related

UniProtKB/Swiss-Prot genetic disease variations for Cerebral Amyloid Angiopathy, App-Related:

76
# Symbol AA change Variation ID SNP ID
1 APP p.Glu693Gln VAR_000017 rs63750579
2 APP p.Glu693Lys VAR_014216 rs63750579
3 APP p.Asp694Asn VAR_014217 rs63749810
4 APP p.Leu705Val VAR_032276 rs63750921

ClinVar genetic disease variations for Cerebral Amyloid Angiopathy, App-Related:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 APP NM_000484.3(APP): c.2077G> C (p.Glu693Gln) single nucleotide variant Pathogenic rs63750579 GRCh37 Chromosome 21, 27264168: 27264168
2 APP NM_000484.3(APP): c.2077G> C (p.Glu693Gln) single nucleotide variant Pathogenic rs63750579 GRCh38 Chromosome 21, 25891856: 25891856
3 APP NM_000484.3(APP): c.2075C> G (p.Ala692Gly) single nucleotide variant Pathogenic rs63750671 GRCh37 Chromosome 21, 27264170: 27264170
4 APP NM_000484.3(APP): c.2075C> G (p.Ala692Gly) single nucleotide variant Pathogenic rs63750671 GRCh38 Chromosome 21, 25891858: 25891858
5 APP NM_000484.3(APP): c.2078A> G (p.Glu693Gly) single nucleotide variant Pathogenic rs63751039 GRCh37 Chromosome 21, 27264167: 27264167
6 APP NM_000484.3(APP): c.2078A> G (p.Glu693Gly) single nucleotide variant Pathogenic rs63751039 GRCh38 Chromosome 21, 25891855: 25891855
7 APP NM_000484.3(APP): c.2077G> A (p.Glu693Lys) single nucleotide variant Pathogenic rs63750579 GRCh37 Chromosome 21, 27264168: 27264168
8 APP NM_000484.3(APP): c.2077G> A (p.Glu693Lys) single nucleotide variant Pathogenic rs63750579 GRCh38 Chromosome 21, 25891856: 25891856
9 APP NM_000484.3(APP): c.2080G> A (p.Asp694Asn) single nucleotide variant Pathogenic rs63749810 GRCh37 Chromosome 21, 27264165: 27264165
10 APP NM_000484.3(APP): c.2080G> A (p.Asp694Asn) single nucleotide variant Pathogenic rs63749810 GRCh38 Chromosome 21, 25891853: 25891853
11 subset of 25 genes:APP NC_000021.8: g.14714507_29216662dup duplication Pathogenic NCBI36 Chromosome 21, 13636378: 28138533
12 subset of 25 genes:APP NC_000021.8: g.14714507_29216662dup duplication Pathogenic GRCh37 Chromosome 21, 14714507: 29216662

Expression for Cerebral Amyloid Angiopathy, App-Related

Search GEO for disease gene expression data for Cerebral Amyloid Angiopathy, App-Related.

Pathways for Cerebral Amyloid Angiopathy, App-Related

Pathways related to Cerebral Amyloid Angiopathy, App-Related according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.98 APP CST3

GO Terms for Cerebral Amyloid Angiopathy, App-Related

Cellular components related to Cerebral Amyloid Angiopathy, App-Related according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.71 APP CST3 GSN SERPINA3
2 extracellular space GO:0005615 9.56 APP CST3 GSN SERPINA3
3 blood microparticle GO:0072562 9.37 GSN SERPINA3
4 ficolin-1-rich granule lumen GO:1904813 9.32 CST3 GSN
5 secretory granule lumen GO:0034774 9.16 GSN SERPINA3
6 extracellular region GO:0005576 9.02 APP CST3 GSN HSPB6 SERPINA3
7 platelet alpha granule lumen GO:0031093 8.96 APP SERPINA3

Biological processes related to Cerebral Amyloid Angiopathy, App-Related according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neutrophil degranulation GO:0043312 9.5 CST3 GSN SERPINA3
2 cellular protein metabolic process GO:0044267 9.43 APP CST3 GSN
3 platelet degranulation GO:0002576 9.37 APP SERPINA3
4 negative regulation of endopeptidase activity GO:0010951 9.33 APP CST3 SERPINA3
5 negative regulation of peptidase activity GO:0010466 9.13 APP CST3 SERPINA3
6 amyloid fibril formation GO:1990000 8.62 APP GSN

Molecular functions related to Cerebral Amyloid Angiopathy, App-Related according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 serine-type endopeptidase inhibitor activity GO:0004867 8.96 APP SERPINA3
2 peptidase inhibitor activity GO:0030414 8.8 APP CST3 SERPINA3

Sources for Cerebral Amyloid Angiopathy, App-Related

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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