FAD
MCID: ERL029
MIFTS: 52

Early-Onset, Autosomal Dominant Alzheimer Disease (FAD)

Categories: Cardiovascular diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Early-Onset, Autosomal Dominant Alzheimer Disease

MalaCards integrated aliases for Early-Onset, Autosomal Dominant Alzheimer Disease:

Name: Early-Onset, Autosomal Dominant Alzheimer Disease 53
Familial Alzheimer Disease 53 59 73
Early-Onset Familial Autosomal Dominant Alzheimer Disease 53 59
Early-Onset Autosomal Dominant Alzheimer Disease 53 59
Eofad 53 59
Alzheimer Disease Familial 29
Fad 53

Characteristics:

Orphanet epidemiological data:

59
early-onset autosomal dominant alzheimer disease
Inheritance: Autosomal dominant; Age of onset: Adult; Age of death: adult;

Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Early-Onset, Autosomal Dominant Alzheimer Disease

NIH Rare Diseases : 53 Early-onset, autosomal dominant Alzheimer disease is a form of Alzheimer disease (AD) that develops before the age of 65. It is diagnosed in families that have more than one member with AD (usually multiple persons in more than one generation) in which the age of onset is consistently before age 60 and often between the ages of 30 and 60 years. In general, AD is a degenerative disease of the brain that causes gradual loss of memory, judgement, and the ability to function socially.  There are three subtypes of early-onset familial AD which are each associated with changes (mutations) in unique genes: (1) Alzheimer disease, type 1 is caused by mutations in the APP gene (2) Alzheimer disease, type 3 is caused by mutations in the PSEN1 gene      (3) Alzheimer disease, type 4 is caused by mutations in the PSEN2 gene.  All subtypes are inherited in an autosomal dominant manner. There is no cure for AD. Treatment is supportive and based on the signs and symptoms present in each person.  

MalaCards based summary : Early-Onset, Autosomal Dominant Alzheimer Disease, also known as familial alzheimer disease, is related to alzheimer disease 2 and alzheimer disease 4. An important gene associated with Early-Onset, Autosomal Dominant Alzheimer Disease is PSEN1 (Presenilin 1), and among its related pathways/superpathways are Presenilin-Mediated Signaling and Neuroscience. The drugs Pramlintide and Islet Amyloid Polypeptide have been mentioned in the context of this disorder. Affiliated tissues include brain and testes, and related phenotypes are intellectual disability and seizures

Related Diseases for Early-Onset, Autosomal Dominant Alzheimer Disease

Diseases in the Alzheimer Disease family:

Alzheimer Disease 2 Alzheimer Disease 16
Alzheimer Disease 5 Alzheimer Disease 6
Alzheimer Disease 7 Alzheimer Disease 4
Alzheimer Disease 8 Alzheimer Disease 3
Alzheimer Disease 9 Alzheimer Disease 10
Alzheimer Disease 11 Alzheimer Disease 12
Alzheimer Disease 13 Alzheimer Disease 14
Alzheimer Disease 15 Alzheimer Disease 17
Alzheimer Disease 18 Alzheimer Disease 19
Alzheimer's Disease 1 Early-Onset, Autosomal Dominant Alzheimer Disease

Diseases related to Early-Onset, Autosomal Dominant Alzheimer Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 alzheimer disease 2 32.9 APP PSEN1 PSEN2
2 alzheimer disease 4 32.1 PSEN1 PSEN2
3 supranuclear palsy, progressive, 1 29.6 APP PSEN1
4 alzheimer disease 29.5 ABCA7 APP PSEN1 PSEN2 SORL1
5 dementia 29.2 APP PSEN1 PSEN2 SORL1 TREM2
6 frontotemporal dementia 29.1 APP PSEN1 PSEN2 TREM2
7 alzheimer disease, familial early-onset, with coexisting amyloid and prion pathology 12.1
8 alzheimer disease 3 11.4
9 alzheimer disease 5 11.4
10 alzheimer disease 7 11.3
11 alzheimer disease 8 11.3
12 alzheimer disease 10 11.3
13 alzheimer disease 12 11.3
14 alzheimer disease 11 11.1
15 aphasia 10.1 APP PSEN1
16 gait apraxia 10.1 APP PSEN1
17 visual agnosia 10.1 PSEN1 PSEN2
18 kohlschutter-tonz syndrome 10.1 APP PSEN1
19 kluver-bucy syndrome 10.1 APP PSEN1
20 familial isolated dilated cardiomyopathy 10.1 PSEN1 PSEN2
21 dopamine beta-hydroxylase deficiency, congenital 10.1 APP PSEN1
22 pick disease of brain 10.0 APP PSEN1
23 cerebral amyloid angiopathy, cst3-related 10.0 APP PSEN1
24 vascular dementia 10.0 APP PSEN1
25 progressive non-fluent aphasia 10.0 PSEN1 TREM2
26 behavioral variant of frontotemporal dementia 10.0 PSEN1 TREM2
27 familial idiopathic basal ganglia calcification 10.0 APP PSEN1 PSEN2
28 semantic dementia 10.0 PSEN1 TREM2
29 dementia, lewy body 9.9 APP PSEN1
30 down syndrome 9.9
31 aging 9.9
32 disease of mental health 9.9 APP PSEN1
33 parkinson disease, late-onset 9.7
34 metachromatic leukodystrophy 9.7
35 alzheimer disease 19 9.7
36 leukodystrophy 9.7
37 corticobasal degeneration 9.7
38 spastic paraparesis 9.7
39 frontotemporal dementia with parkinsonism-17 9.7
40 amyotrophic lateral sclerosis 1 9.7 APP PSEN1 TREM2

Graphical network of the top 20 diseases related to Early-Onset, Autosomal Dominant Alzheimer Disease:



Diseases related to Early-Onset, Autosomal Dominant Alzheimer Disease

Symptoms & Phenotypes for Early-Onset, Autosomal Dominant Alzheimer Disease

Human phenotypes related to Early-Onset, Autosomal Dominant Alzheimer Disease:

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 occasional (7.5%) Occasional (29-5%) HP:0001249
2 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
4 hallucinations 59 32 hallmark (90%) Very frequent (99-80%) HP:0000738
5 hypertonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001276
6 abnormality of vision 59 32 occasional (7.5%) Occasional (29-5%) HP:0000504
7 myoclonus 59 32 hallmark (90%) Very frequent (99-80%) HP:0001336
8 cerebral cortical atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0002120
9 memory impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0002354
10 aphasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002381
11 agitation 59 32 hallmark (90%) Very frequent (99-80%) HP:0000713
12 dysgraphia 59 32 occasional (7.5%) Occasional (29-5%) HP:0010526
13 abnormal social behavior 59 32 hallmark (90%) Very frequent (99-80%) HP:0012433
14 oculomotor apraxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000657
15 confusion 59 32 hallmark (90%) Very frequent (99-80%) HP:0001289
16 parkinsonism 59 32 hallmark (90%) Very frequent (99-80%) HP:0001300
17 neurofibrillary tangles 59 32 hallmark (90%) Very frequent (99-80%) HP:0002185
18 language impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0002463
19 deposits immunoreactive to beta-amyloid protein 59 32 hallmark (90%) Very frequent (99-80%) HP:0003791
20 disinhibition 59 32 frequent (33%) Frequent (79-30%) HP:0000734
21 finger agnosia 59 32 occasional (7.5%) Occasional (29-5%) HP:0010525
22 semantic dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0030219
23 apraxia 59 Occasional (29-5%)
24 dementia 59 Very frequent (99-80%)
25 neurodevelopmental abnormality 59 Very frequent (99-80%)
26 abnormality of higher mental function 59 Occasional (29-5%)

MGI Mouse Phenotypes related to Early-Onset, Autosomal Dominant Alzheimer Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.43 ABCA7 APP PSEN1 PSEN2 SORL1 TREM2
2 homeostasis/metabolism MP:0005376 9.1 ABCA7 APP PSEN1 PSEN2 SORL1 TREM2

Drugs & Therapeutics for Early-Onset, Autosomal Dominant Alzheimer Disease

Drugs for Early-Onset, Autosomal Dominant Alzheimer Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Pramlintide Approved, Investigational Early Phase 1 151126-32-8
2 Islet Amyloid Polypeptide Early Phase 1
3 Anti-Obesity Agents Early Phase 1
4 Hypoglycemic Agents Early Phase 1
5 Appetite Depressants Early Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic Studies in Alzheimer's Disease Completed NCT00001235
2 The Chinese Familial Alzheimer's Network Recruiting NCT03657732
3 China Cognition and Aging Study Recruiting NCT03653156
4 Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease Enrolling by invitation NCT03560960 Early Phase 1 Pramlintide challenge test

Search NIH Clinical Center for Early-Onset, Autosomal Dominant Alzheimer Disease

Genetic Tests for Early-Onset, Autosomal Dominant Alzheimer Disease

Genetic tests related to Early-Onset, Autosomal Dominant Alzheimer Disease:

# Genetic test Affiliating Genes
1 Alzheimer Disease Familial 29

Anatomical Context for Early-Onset, Autosomal Dominant Alzheimer Disease

MalaCards organs/tissues related to Early-Onset, Autosomal Dominant Alzheimer Disease:

41
Brain, Testes

Publications for Early-Onset, Autosomal Dominant Alzheimer Disease

Articles related to Early-Onset, Autosomal Dominant Alzheimer Disease:

(show top 50) (show all 114)
# Title Authors Year
1
A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. ( 29988083 )
2018
2
Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1. ( 29466804 )
2018
3
Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration. ( 29070659 )
2017
4
Polygenic risk scores in familial Alzheimer disease. ( 28213371 )
2017
5
Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene. ( 28595629 )
2017
6
Expression of familial Alzheimer disease presenilin 1 gene attenuates vesicle traffic and reduces peptide secretion in cultured astrocytes devoid of pathologic tissue environment. ( 26462451 )
2016
7
Autophagic and lysosomal defects in human tauopathies: analysis of post-mortem brain from patients with familial Alzheimer disease, corticobasal degeneration and progressive supranuclear palsy. ( 26936765 )
2016
8
The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease. ( 27533593 )
2016
9
Presymptomatic cortical thinning in familial Alzheimer disease: A longitudinal MRI study. ( 27733562 )
2016
10
Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 With Familial Alzheimer Disease Among Caribbean Hispanics. ( 26214276 )
2015
11
Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate I^-Secretase Activities. ( 26559975 )
2015
12
Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study. ( 27092264 )
2015
13
Cell signaling abnormalities may drive neurodegeneration in familial Alzheimer disease. ( 23436150 )
2014
14
A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease. ( 24582897 )
2014
15
Relative ratio and level of amyloid-I^ 42 surrogate in cerebrospinal fluid of familial Alzheimer disease patients with presenilin 1 mutations. ( 24192669 )
2014
16
Clinical and neuropathological findings in a patient with familial Alzheimer disease showing a mutation in the PSEN1 gene. ( 22882713 )
2013
17
The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study. ( 24049139 )
2013
18
The mechanism of I^-Secretase dysfunction in familial Alzheimer disease. ( 22505025 )
2012
19
Evidence for premature lipid raft aging in APP/PS1 double-transgenic mice, a model of familial Alzheimer disease. ( 22975585 )
2012
20
Familial Alzheimer disease presenilin-1 mutations alter the active site conformation of I^-secretase. ( 22461631 )
2012
21
Proteomic changes in cerebrospinal fluid of presymptomatic and affected persons carrying familial Alzheimer disease mutations. ( 22232349 )
2012
22
Exploratory data from complete genomes of familial alzheimer disease age-at-onset outliers. ( 22829467 )
2012
23
Genetic counseling for early-onset familial Alzheimer disease in large Aboriginal kindred from a remote community in British Columbia: unique challenges and possible solutions. ( 20927575 )
2011
24
[Familial Alzheimer disease]. ( 22755192 )
2011
25
Linkage analysis of autopsy-confirmed familial Alzheimer disease supports an Alzheimer disease locus in 8q24. ( 21273770 )
2011
26
Event-related potential markers of brain changes in preclinical familial Alzheimer disease. ( 21775732 )
2011
27
A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity. ( 20460383 )
2010
28
A DNA methylation study of the amyloid precursor protein gene in several brain regions from patients with familial Alzheimer disease. ( 20919856 )
2010
29
Aberrant amyloid precursor protein (APP) processing in hereditary forms of Alzheimer disease caused by APP familial Alzheimer disease mutations can be rescued by mutations in the APP GxxxG motif. ( 20452985 )
2010
30
Effects of the English (H6R) and Tottori (D7N) familial Alzheimer disease mutations on amyloid beta-protein assembly and toxicity. ( 20452980 )
2010
31
Familial Alzheimer disease in Canada. ( 20481260 )
2010
32
Caspase-6 activation in familial alzheimer disease brains carrying amyloid precursor protein or presenilin i or presenilin II mutations. ( 19915487 )
2009
33
Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome. ( 20008652 )
2009
34
Cortical event-related potentials in preclinical familial Alzheimer disease. ( 19917987 )
2009
35
Intramembrane proteolysis of GXGD-type aspartyl proteases is slowed by a familial Alzheimer disease-like mutation. ( 18768471 )
2008
36
Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta. ( 18430735 )
2008
37
Early onset familial Alzheimer Disease with spastic paraparesis, dysarthria, and seizures and N135S mutation in PSEN1. ( 18580586 )
2008
38
Biochemical markers in persons with preclinical familial Alzheimer disease. ( 18509095 )
2008
39
Mutation negative "early-onset familial Alzheimer disease": consider screening for tau gene mutations. ( 18525295 )
2008
40
Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation. ( 17962197 )
2008
41
Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. ( 17431506 )
2007
42
Variability of age at onset in siblings with familial Alzheimer disease. ( 18071037 )
2007
43
The heritability of abstract reasoning in Caribbean Latinos with familial Alzheimer disease. ( 17938569 )
2007
44
The Tottori (D7N) and English (H6R) familial Alzheimer disease mutations accelerate Abeta fibril formation without increasing protofibril formation. ( 17170111 )
2007
45
Familial Alzheimer disease in Latinos: interaction between APOE, stroke, and estrogen replacement. ( 16401842 )
2006
46
MRS shows abnormalities before symptoms in familial Alzheimer disease. ( 16534109 )
2006
47
Apolipoprotein E epsilon4 and age at onset of sporadic and familial Alzheimer disease in Caribbean Hispanics. ( 17101827 )
2006
48
LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. ( 16957580 )
2006
49
Formation of tau inclusions in knock-in mice with familial Alzheimer disease (FAD) mutation of presenilin 1 (PS1). ( 16377636 )
2006
50
Lewy body pathology in familial Alzheimer disease: evidence for disease- and mutation-specific pathologic phenotype. ( 16533963 )
2006

Variations for Early-Onset, Autosomal Dominant Alzheimer Disease

Expression for Early-Onset, Autosomal Dominant Alzheimer Disease

Search GEO for disease gene expression data for Early-Onset, Autosomal Dominant Alzheimer Disease.

Pathways for Early-Onset, Autosomal Dominant Alzheimer Disease

Pathways related to Early-Onset, Autosomal Dominant Alzheimer Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.7 APP PSEN1 PSEN2
2 11.56 APP PSEN1 PSEN2 SORL1 TREM2
3
Show member pathways
11.25 APP PSEN1
4 11.17 APP PSEN1 PSEN2
5 10.99 APP PSEN1 PSEN2
6 10.84 PSEN1 PSEN2
7 10.49 APP PSEN1 PSEN2
8 10.02 PSEN1 PSEN2

GO Terms for Early-Onset, Autosomal Dominant Alzheimer Disease

Cellular components related to Early-Onset, Autosomal Dominant Alzheimer Disease according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.87 ABCA7 APP PSEN1 PSEN2 SORL1 TOMM40
2 integral component of plasma membrane GO:0005887 9.8 APP PSEN1 PSEN2 SORL1
3 Golgi membrane GO:0000139 9.56 ABCA7 PSEN1 PSEN2 SORL1
4 Golgi apparatus GO:0005794 9.55 ABCA7 APP PSEN1 PSEN2 SORL1
5 neuromuscular junction GO:0031594 9.48 APP PSEN1
6 rough endoplasmic reticulum GO:0005791 9.46 APP PSEN1
7 integral component of presynaptic membrane GO:0099056 9.43 PSEN1 PSEN2
8 dendritic shaft GO:0043198 9.4 APP PSEN1
9 smooth endoplasmic reticulum GO:0005790 9.37 APP PSEN1
10 ciliary rootlet GO:0035253 8.96 APP PSEN1
11 nuclear envelope lumen GO:0005641 8.62 APP SORL1
12 membrane GO:0016020 10.05 ABCA7 APP PSEN1 PSEN2 SORL1 TOMM40

Biological processes related to Early-Onset, Autosomal Dominant Alzheimer Disease according to GeneCards Suite gene sharing:

(show all 30)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.77 ABCA7 APP TREM2
2 cellular protein metabolic process GO:0044267 9.75 APP PSEN1 SORL1
3 Notch signaling pathway GO:0007219 9.7 APP PSEN1 PSEN2
4 positive regulation of catalytic activity GO:0043085 9.65 PSEN1 PSEN2
5 cholesterol metabolic process GO:0008203 9.64 APP SORL1
6 memory GO:0007613 9.64 ABCA7 PSEN1
7 forebrain development GO:0030900 9.63 APP PSEN1
8 positive regulation of protein binding GO:0032092 9.63 APP PSEN1
9 learning or memory GO:0007611 9.62 APP PSEN1
10 protein processing GO:0016485 9.62 PSEN1 PSEN2
11 synapse organization GO:0050808 9.61 APP PSEN1
12 neuron apoptotic process GO:0051402 9.61 APP PSEN1
13 cellular response to amyloid-beta GO:1904646 9.6 APP PSEN1
14 positive regulation of phosphorylation GO:0042327 9.58 APP PSEN1
15 membrane protein ectodomain proteolysis GO:0006509 9.57 PSEN1 PSEN2
16 regulation of protein binding GO:0043393 9.56 APP PSEN1
17 protein maturation GO:0051604 9.55 PSEN1 SORL1
18 amyloid-beta metabolic process GO:0050435 9.54 PSEN1 PSEN2
19 astrocyte activation GO:0048143 9.51 APP PSEN1
20 negative regulation of amyloid-beta formation GO:1902430 9.49 ABCA7 SORL1
21 neuron projection maintenance GO:1990535 9.48 APP PSEN1
22 Notch receptor processing GO:0007220 9.46 PSEN1 PSEN2
23 amyloid precursor protein catabolic process GO:0042987 9.43 PSEN1 PSEN2
24 modulation of age-related behavioral decline GO:0090647 9.4 APP PSEN1
25 Notch receptor processing, ligand-dependent GO:0035333 9.37 PSEN1 PSEN2
26 negative regulation of low-density lipoprotein receptor activity GO:1905598 9.32 APP PSEN1
27 positive regulation of amyloid fibril formation GO:1905908 9.26 APP PSEN1
28 regulation of epidermal growth factor-activated receptor activity GO:0007176 9.16 APP PSEN1
29 astrocyte activation involved in immune response GO:0002265 8.96 APP PSEN1
30 smooth endoplasmic reticulum calcium ion homeostasis GO:0051563 8.62 APP PSEN1

Molecular functions related to Early-Onset, Autosomal Dominant Alzheimer Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endopeptidase activity GO:0004175 9.16 PSEN1 PSEN2
2 aspartic-type endopeptidase activity GO:0004190 8.96 PSEN1 PSEN2
3 aspartic endopeptidase activity, intramembrane cleaving GO:0042500 8.62 PSEN1 PSEN2

Sources for Early-Onset, Autosomal Dominant Alzheimer Disease

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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