CAA-APP
MCID: CRB193
MIFTS: 48

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 57 75 29 6 40
Hchwad 57 12 75
Cerebral Amyloid Angiopathy, Dutch, Italian, Iowa, Flemish, Arctic Variants 57 13
Amyloidosis, Hereditary, with Cerebral Hemorrhage, Dutch Variant 57 12
Cerebral Amyloid Angiopathy, App-Related, Italian Variant 57 12
Cerebral Amyloid Angiopathy, App-Related, Flemish Variant 57 12
Cerebral Amyloid Angiopathy, App-Related, Arctic Variant 57 12
Cerebral Amyloid Angiopathy, App-Related, Dutch Variant 57 12
Cerebral Amyloid Angiopathy, App-Related, Iowa Variant 57 12
Amyloidosis, Cerebroarterial, App-Related 57 12
App-Related Cerebral Amyloid Angiopathy 12 15
Hchwa-D 59 75
Familial Occipital Calcifications with Hemorrhagic Strokes Leukoencephalopathy Arterial Dysplasia Dementia 75
Amyloidosis, Hereditary, with Cerebral Hemorrhage, Dutch Variant; Hchwad 57
Hereditary Cerebral Hemorrhage with Amyloidosis, Piedmont Type 59
Hereditary Cerebral Hemorrhage with Amyloidosis, Flemish Type 59
Hereditary Cerebral Hemorrhage with Amyloidosis, Italian Type 59
Amyloidosis Hereditary with Cerebral Hemorrhage Dutch Variant 75
Hereditary Cerebral Hemorrhage with Amyloidosis, Arctic Type 59
Hereditary Cerebral Hemorrhage with Amyloidosis Italian Type 75
Cerebral Hemorrhage with Amyloidosis, Hereditary, Dutch Type 73
Hereditary Cerebral Hemorrhage with Amyloidosis, Dutch Type 59
Hereditary Cerebral Hemorrhage with Amyloidosis, Iowa Type 59
Hereditary Cerebral Hemorrhage with Amyloidosis Dutch Type 75
Cerebral Amyloid Angiopathy App-Related Flemish Variant 75
Cerebral Amyloid Angiopathy App-Related Italian Variant 75
Cerebral Amyloid Angiopathy App-Related Arctic Variant 75
Cerebral Amyloid Angiopathy App-Related Dutch Variant 75
Cerebral Amyloid Angiopathy App-Related Iowa Variant 75
Hereditary Cerebral Amyloid Angiopathy Dutch Type 75
Amyloidosis Cerebroarterial App-Related 75
Abeta Amyloidosis, Piedmont Type 59
Abeta Amyloidosis, Flemish Type 59
Abeta Amyloidosis, Italian Type 59
Abeta Amyloidosis, Arctic Type 59
Abetaa21g-Related Amyloidosis 59
Abetal34v-Related Amyloidosis 59
Abeta Amyloidosis, Dutch Type 59
Abeta Amyloidosis, Iowa Type 59
Abetaa21g Amyloidosis 59
Abetae22k Amyloidosis 59
Abetae22g Amyloidosis 59
Abetad23n Amyloidosis 59
Abetal34v Amyloidosis 59
Abetae22q Amyloidosis 59
Hchwa, Piedmont Type 59
Hchwa, Flemish Type 59
Hchwa, Italian Type 59
Hchwa, Arctic Type 59
Hchwa, Dutch Type 59
Hchwa, Iowa Type 59
Fochs-Ladd 75
Caa-App 75

Characteristics:

Orphanet epidemiological data:

59
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:

57
Inheritance:
autosomal dominant

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


HPO:

32
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 : 75 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 are Wnt Signaling Pathways: beta-Catenin-dependent Wnt Signaling and Diseases of glycosylation. Affiliated tissues include brain, bone and cerebellum, and related phenotypes are intellectual disability and seizures

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

OMIM : 57 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

Diseases in the Hereditary Cerebral Amyloid Angiopathy family:

Cerebral Amyloid Angiopathy, Cst3-Related Cerebral Amyloid Angiopathy, Itm2b-Related, 2
Cerebral Amyloid Angiopathy, Itm2b-Related, 1 Cerebral Amyloid Angiopathy, App-Related

Diseases related to Cerebral Amyloid Angiopathy, App-Related via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cerebral hemorrhage 30.8 APP CST3
2 amyloidosis 30.6 APP CST3
3 hereditary cerebral amyloid angiopathy 30.2 APP CST3
4 cerebral amyloid angiopathy, cst3-related 30.0 APP CST3 HSPB6 HSPB8
5 alzheimer disease 10.5
6 dementia 10.3
7 hemorrhage, intracerebral 10.0 APP CST3
8 vascular dementia 9.9 APP CST3
9 amyotrophic lateral sclerosis 1 9.7 APP CST3 HSPB8

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

Symptoms via clinical synopsis from OMIM:

57
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

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

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 59 32 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001250
3 gait disturbance 59 32 hallmark (90%) Very frequent (99-80%) HP:0001288
4 dysphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002015
5 cerebral calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002514
6 behavioral abnormality 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Frequent (79-30%),Very frequent (99-80%) HP:0000708
7 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
8 myoclonus 59 32 hallmark (90%) Very frequent (99-80%) HP:0001336
9 migraine 59 32 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0002076
10 memory impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0002354
11 paresthesia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003401
12 febrile seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002373
13 dementia 59 32 hallmark (90%) Frequent (79-30%),Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%) HP:0000726
14 coma 59 32 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0001259
15 stroke 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%) HP:0001297
16 headache 59 32 hallmark (90%) Very frequent (99-80%) HP:0002315
17 cerebral hemorrhage 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%),Very frequent (99-80%) HP:0001342
18 sensory impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0003474
19 cerebral amyloid angiopathy 59 32 frequent (33%) Frequent (79-30%) HP:0011970
20 cerebral ischemia 32 HP:0002637
21 death in early adulthood 59 Occasional (29-5%)
22 abnormality of the cerebral vasculature 59 Very frequent (99-80%),Frequent (79-30%)
23 mental deterioration 59 Frequent (79-30%),Very frequent (99-80%)
24 cerebellar hemorrhage 32 HP:0011695
25 recurrent cerebral hemorrhage 32 HP:0004968
26 tortuous cerebral arteries 32 HP:0004938

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 29 APP

Anatomical Context for Cerebral Amyloid Angiopathy, App-Related

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

41
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:

75
# 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

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 lysosomal lumen GO:0043202 9.16 GPC1 SDC2
2 endoplasmic reticulum lumen GO:0005788 9.13 APP CST3 SDC2
3 Golgi lumen GO:0005796 8.8 APP GPC1 SDC2

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

# Name GO ID Score Top Affiliating Genes
1 post-translational protein modification GO:0043687 9.43 APP CST3 SDC2
2 negative regulation of endopeptidase activity GO:0010951 9.4 APP CST3
3 negative regulation of peptidase activity GO:0010466 9.37 APP CST3
4 retinoid metabolic process GO:0001523 9.32 GPC1 SDC2
5 glycosaminoglycan biosynthetic process GO:0006024 9.16 GPC1 SDC2
6 glycosaminoglycan catabolic process GO:0006027 8.96 GPC1 SDC2
7 cellular protein metabolic process GO:0044267 8.8 APP CST3 SDC2

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

# Name GO ID Score Top Affiliating Genes
1 peptidase inhibitor activity GO:0030414 8.96 APP CST3
2 identical protein binding GO:0042802 8.92 APP CST3 HSPB8 SDC2

Sources for Cerebral Amyloid Angiopathy, App-Related

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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