AD4
MCID: ALZ054
MIFTS: 45

Alzheimer Disease 4 (AD4)

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

Aliases & Classifications for Alzheimer Disease 4

MalaCards integrated aliases for Alzheimer Disease 4:

Name: Alzheimer Disease 4 57 12 53 75 73
Ad4 57 12 53 75
Alzheimer Disease, Type 4 29 6 40
Alzheimer Disease-4 57 13
Alzheimer Disease Familial Type 4 53
Alzheimer Disease, Familial, 4 57
Alzheimer Disease, Familial4 12
Alzheimer Disease Type 4 53
Alzheimer's Disease 4 12

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
early onset, between 35-60 years
accounts for <2% of patients with alzheimer's disease
see entry for general information on alzheimer disease


HPO:

32
alzheimer disease 4:
Inheritance autosomal dominant inheritance
Onset and clinical course middle age onset


Classifications:



External Ids:

OMIM 57 606889
Disease Ontology 12 DOID:0110040
MedGen 42 C1847200
MeSH 44 D000544
UMLS 73 C1847200

Summaries for Alzheimer Disease 4

UniProtKB/Swiss-Prot : 75 Alzheimer disease 4: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid- beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.

MalaCards based summary : Alzheimer Disease 4, also known as ad4, is related to early-onset, autosomal dominant alzheimer disease and tardive dyskinesia. An important gene associated with Alzheimer Disease 4 is PSEN2 (Presenilin 2), and among its related pathways/superpathways are Development HGF signaling pathway and Neuroscience. The drugs Benzocaine and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include brain, and related phenotypes are dementia and senile plaques

Disease Ontology : 12 An Alzheimer's disease that has material basis in a mutation in the presenilin-2 gene (PSEN2) on chromosome 1q42.

Description from OMIM: 606889

Related Diseases for Alzheimer Disease 4

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 Alzheimer Disease 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
# Related Disease Score Top Affiliating Genes
1 early-onset, autosomal dominant alzheimer disease 31.6 PSEN1 PSEN2
2 tardive dyskinesia 10.0
3 alzheimer disease 5 10.0
4 alzheimer disease 7 10.0
5 beta-thalassemia 10.0
6 hepatitis 10.0
7 hepatitis b 10.0
8 thalassemia 10.0
9 visual agnosia 9.9 PSEN1 PSEN2
10 familial isolated dilated cardiomyopathy 9.9 PSEN1 PSEN2
11 alexia 9.9 APOE PSEN1
12 gait apraxia 9.9 APOE PSEN1
13 semantic dementia 9.9 APOE PSEN1
14 kohlschutter-tonz syndrome 9.9 APOE PSEN1
15 aphasia 9.9 APOE PSEN1
16 pick disease of brain 9.9 APOE PSEN1
17 cerebral amyloid angiopathy, cst3-related 9.9 APOE PSEN1
18 supranuclear palsy, progressive, 1 9.9 APOE PSEN1
19 vascular dementia 9.9 APOE PSEN1
20 dementia, lewy body 9.8 APOE PSEN1
21 speech and communication disorders 9.8 APOE PSEN1
22 disease of mental health 9.8 APOE PSEN1
23 amyloidosis 9.8 APOE PSEN1
24 alzheimer disease 9.8 APOE PSEN1 PSEN2
25 nervous system disease 9.8 APOE PSEN1
26 familial idiopathic basal ganglia calcification 9.8 APOE PSEN1 PSEN2
27 alzheimer disease 2 9.8 APOE PSEN1 PSEN2
28 frontotemporal dementia 9.7 APOE PSEN1 PSEN2
29 dementia 9.7 APOE PSEN1 PSEN2
30 central nervous system disease 9.7 APOE PSEN1

Graphical network of the top 20 diseases related to Alzheimer Disease 4:



Diseases related to Alzheimer Disease 4

Symptoms & Phenotypes for Alzheimer Disease 4

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
sleep-wake cycle disturbance
presenile dementia

Laboratory Abnormalities:
neurofibrillary tangles and neuritic senile plaques rare
severe amyloid angiopathy


Clinical features from OMIM:

606889

Human phenotypes related to Alzheimer Disease 4:

32
# Description HPO Frequency HPO Source Accession
1 dementia 32 HP:0000726
2 senile plaques 32 HP:0100256
3 sleep-wake cycle disturbance 32 HP:0006979
4 alzheimer disease 32 HP:0002511
5 cerebral amyloid angiopathy 32 HP:0011970

MGI Mouse Phenotypes related to Alzheimer Disease 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.46 APOE CDK1 PSEN1 PSEN2
2 mortality/aging MP:0010768 9.35 APOE CDK1 GSS PSEN1 PSEN2
3 vision/eye MP:0005391 8.92 APOE CDK1 PSEN1 PSEN2

Drugs & Therapeutics for Alzheimer Disease 4

Drugs for Alzheimer Disease 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Benzocaine Approved, Investigational Phase 3 94-09-7, 1994-09-7 2337
2
Miconazole Approved, Investigational, Vet_approved Phase 3 22916-47-8 4189
3 tannic acid Approved Phase 3
4 Dermatologic Agents Phase 3
5 Calcineurin Inhibitors Phase 3
6 Immunosuppressive Agents Phase 3
7 Antirheumatic Agents Phase 3
8 Anti-Infective Agents Phase 3,Not Applicable
9 Antifungal Agents Phase 3
10 Cyclosporins Phase 3
11 Immunologic Factors Phase 3,Phase 1
12
Aluminum hydroxide Approved, Investigational Phase 1 21645-51-2
13 Vaccines Phase 1
14 Antibodies Phase 1
15 Immunoglobulins Phase 1
16 Monophosphoryl lipid A Phase 1
17 Krestin Phase 1
18 Nucleic Acid Synthesis Inhibitors Not Applicable
19 Anti-Bacterial Agents Not Applicable
20 Charcoal Not Applicable
21 Fluoroquinolones Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable Recruiting NCT03428100 Phase 3 Baricitinib;Placebo;Topical corticosteroid
2 Intranasal AD4-H5-VTN as an Adenovirus Vaccine Completed NCT01806909 Phase 1
3 Clinical Trial of HIV Vaccine Combinations in Healthy Men and Women Recruiting NCT03408262 Phase 1
4 Experimental AD4-H5-VTN Vaccine in Healthy Volunteers Completed NCT01443936 Phase 1
5 Safety and Immunogenicity of Replication-Competent Adenovirus 4-vectored Vaccine for Avian Influenza H5N1 Completed NCT01006798 Phase 1
6 A Phase 1 Ascending Dose Study to Assess the Safety and Immunogenicity of Adenovirus Anthrax Vector Candidate Vaccines Completed NCT01979406 Phase 1
7 A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047 Terminated NCT03160339 Phase 1
8 Study of Safety and Immunogenicity of HIV Vaccines in Healthy Volunteers Active, not recruiting NCT01989533 Phase 1
9 Study to Evaluate the Safety and Immunogenicity of Orally-administered HIV Vaccine in Healthy, HIV-uninfected Adult Participants Active, not recruiting NCT02771730 Phase 1
10 Safety and Efficacy of DAV132 in Patients at High-Risk for Clostridium Difficile Infection (CDI) Recruiting NCT03710694 Not Applicable

Search NIH Clinical Center for Alzheimer Disease 4

Genetic Tests for Alzheimer Disease 4

Genetic tests related to Alzheimer Disease 4:

# Genetic test Affiliating Genes
1 Alzheimer Disease, Type 4 29 APOE PSEN2

Anatomical Context for Alzheimer Disease 4

MalaCards organs/tissues related to Alzheimer Disease 4:

41
Brain

Publications for Alzheimer Disease 4

Articles related to Alzheimer Disease 4:

# Title Authors Year
1
Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells. ( 28202838 )
2017
2
N-acetylcysteine amide (AD4) reduces cocaine-induced reinstatement. ( 27469021 )
2016
3
N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells. ( 18082636 )
2008
4
Emergence of a new human adenovirus type 4 (Ad4) genotype: identification of a novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates from US military recruits. ( 16406799 )
2006
5
Replication and immunogenicity of Ad7-, Ad4-, and Ad5-hepatitis B virus surface antigen recombinants, with or without a portion of E3 region, in chimpanzees. ( 9139496 )
1997

Variations for Alzheimer Disease 4

UniProtKB/Swiss-Prot genetic disease variations for Alzheimer Disease 4:

75
# Symbol AA change Variation ID SNP ID
1 PSEN2 p.Asn141Ile VAR_006462 rs63750215
2 PSEN2 p.Met239Val VAR_006463 rs28936379
3 PSEN2 p.Val148Ile VAR_007958 rs63750812
4 PSEN2 p.Thr122Pro VAR_009214 rs63749851
5 PSEN2 p.Met239Ile VAR_009215 rs63749884

ClinVar genetic disease variations for Alzheimer Disease 4:

6 (show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 PSEN2 NM_000447.2(PSEN2): c.422A> T (p.Asn141Ile) single nucleotide variant Pathogenic rs63750215 GRCh37 Chromosome 1, 227073304: 227073304
2 PSEN2 NM_000447.2(PSEN2): c.422A> T (p.Asn141Ile) single nucleotide variant Pathogenic rs63750215 GRCh38 Chromosome 1, 226885603: 226885603
3 PSEN2 NM_000447.2(PSEN2): c.715A> G (p.Met239Val) single nucleotide variant Pathogenic rs28936379 GRCh37 Chromosome 1, 227076678: 227076678
4 PSEN2 NM_000447.2(PSEN2): c.715A> G (p.Met239Val) single nucleotide variant Pathogenic rs28936379 GRCh38 Chromosome 1, 226888977: 226888977
5 PSEN2 NM_000447.2(PSEN2): c.1316A> C (p.Asp439Ala) single nucleotide variant Uncertain significance rs63750110 GRCh37 Chromosome 1, 227083249: 227083249
6 PSEN2 NM_000447.2(PSEN2): c.1316A> C (p.Asp439Ala) single nucleotide variant Uncertain significance rs63750110 GRCh38 Chromosome 1, 226895548: 226895548
7 PSEN2 NM_000447.2(PSEN2): c.1289C> T (p.Thr430Met) single nucleotide variant Pathogenic rs63750666 GRCh37 Chromosome 1, 227083222: 227083222
8 PSEN2 NM_000447.2(PSEN2): c.1289C> T (p.Thr430Met) single nucleotide variant Pathogenic rs63750666 GRCh38 Chromosome 1, 226895521: 226895521
9 PSEN2 NM_000447.2(PSEN2): c.364A> C (p.Thr122Pro) single nucleotide variant Likely pathogenic rs63749851 GRCh37 Chromosome 1, 227073246: 227073246
10 PSEN2 NM_000447.2(PSEN2): c.364A> C (p.Thr122Pro) single nucleotide variant Likely pathogenic rs63749851 GRCh38 Chromosome 1, 226885545: 226885545
11 PSEN2 NM_000447.2(PSEN2): c.717G> A (p.Met239Ile) single nucleotide variant Pathogenic rs63749884 GRCh37 Chromosome 1, 227076680: 227076680
12 PSEN2 NM_000447.2(PSEN2): c.717G> A (p.Met239Ile) single nucleotide variant Pathogenic rs63749884 GRCh38 Chromosome 1, 226888979: 226888979
13 PSEN2 NM_000447.2(PSEN2): c.365C> G (p.Thr122Arg) single nucleotide variant Pathogenic rs28936380 GRCh37 Chromosome 1, 227073247: 227073247
14 PSEN2 NM_000447.2(PSEN2): c.365C> G (p.Thr122Arg) single nucleotide variant Pathogenic rs28936380 GRCh38 Chromosome 1, 226885546: 226885546
15 PSEN2 NM_000447.2(PSEN2): c.389C> T (p.Ser130Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs63750197 GRCh37 Chromosome 1, 227073271: 227073271
16 PSEN2 NM_000447.2(PSEN2): c.389C> T (p.Ser130Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs63750197 GRCh38 Chromosome 1, 226885570: 226885570
17 PSEN2 NM_000447.2(PSEN2): c.254C> T (p.Ala85Val) single nucleotide variant Pathogenic rs63750048 GRCh37 Chromosome 1, 227071518: 227071518
18 PSEN2 NM_000447.2(PSEN2): c.254C> T (p.Ala85Val) single nucleotide variant Pathogenic rs63750048 GRCh38 Chromosome 1, 226883817: 226883817
19 PSEN1 NG_007386.2: g.73292_77847del4556 deletion Pathogenic GRCh37 Chromosome 14, 73671470: 73676025
20 PSEN1 NG_007386.2: g.73292_77847del4556 deletion Pathogenic GRCh38 Chromosome 14, 73204762: 73209317
21 PSEN1 NM_000021.3(PSEN1): c.806G> A (p.Arg269His) single nucleotide variant Pathogenic rs63750900 GRCh37 Chromosome 14, 73664775: 73664775
22 PSEN1 NM_000021.3(PSEN1): c.806G> A (p.Arg269His) single nucleotide variant Pathogenic rs63750900 GRCh38 Chromosome 14, 73198067: 73198067
23 PSEN2 NM_000447.2(PSEN2): c.185G> A (p.Arg62His) single nucleotide variant Benign/Likely benign rs58973334 GRCh37 Chromosome 1, 227071449: 227071449
24 PSEN2 NM_000447.2(PSEN2): c.185G> A (p.Arg62His) single nucleotide variant Benign/Likely benign rs58973334 GRCh38 Chromosome 1, 226883748: 226883748
25 PSEN2 NM_000447.2(PSEN2): c.129C> T (p.Asn43=) single nucleotide variant Benign/Likely benign rs6759 GRCh38 Chromosome 1, 226882036: 226882036
26 PSEN2 NM_000447.2(PSEN2): c.129C> T (p.Asn43=) single nucleotide variant Benign/Likely benign rs6759 GRCh37 Chromosome 1, 227069737: 227069737
27 PSEN2 NM_000447.2(PSEN2): c.261C> T (p.His87=) single nucleotide variant Benign/Likely benign rs1046240 GRCh38 Chromosome 1, 226883824: 226883824
28 PSEN2 NM_000447.2(PSEN2): c.261C> T (p.His87=) single nucleotide variant Benign/Likely benign rs1046240 GRCh37 Chromosome 1, 227071525: 227071525
29 PSEN2 NM_000447.2(PSEN2): c.903G> T (p.Thr301=) single nucleotide variant Benign/Likely benign rs6426553 GRCh38 Chromosome 1, 226891294: 226891294
30 PSEN2 NM_000447.2(PSEN2): c.903G> T (p.Thr301=) single nucleotide variant Benign/Likely benign rs6426553 GRCh37 Chromosome 1, 227078995: 227078995
31 PSEN2 NM_000447.2(PSEN2): c.886+2_886+4delTGA deletion Likely pathogenic GRCh37 Chromosome 1, 227077836: 227077838
32 PSEN2 NM_000447.2(PSEN2): c.886+2_886+4delTGA deletion Likely pathogenic GRCh38 Chromosome 1, 226890135: 226890137
33 PSEN2 NC_000001.11: g.(?_226881888)_(226895599_?)del deletion Pathogenic GRCh38 Chromosome 1, 226881888: 226895599
34 PSEN2 NC_000001.11: g.(?_226881888)_(226895599_?)del deletion Pathogenic GRCh37 Chromosome 1, 227069589: 227083300
35 PSEN2 NM_000447.2(PSEN2): c.132T> A (p.Thr44=) single nucleotide variant Benign rs143227762 GRCh38 Chromosome 1, 226882039: 226882039
36 PSEN2 NM_000447.2(PSEN2): c.132T> A (p.Thr44=) single nucleotide variant Benign rs143227762 GRCh37 Chromosome 1, 227069740: 227069740
37 PSEN2 NM_000447.2(PSEN2): c.1176C> T (p.Phe392=) single nucleotide variant Benign rs115652716 GRCh38 Chromosome 1, 226894110: 226894110
38 PSEN2 NM_000447.2(PSEN2): c.1176C> T (p.Phe392=) single nucleotide variant Benign rs115652716 GRCh37 Chromosome 1, 227081811: 227081811
39 PSEN2 NM_000447.2(PSEN2): c.423C> T (p.Asn141=) single nucleotide variant Benign rs116003409 GRCh38 Chromosome 1, 226885604: 226885604
40 PSEN2 NM_000447.2(PSEN2): c.423C> T (p.Asn141=) single nucleotide variant Benign rs116003409 GRCh37 Chromosome 1, 227073305: 227073305
41 PSEN2 NM_000447.2(PSEN2): c.279G> C (p.Val93=) single nucleotide variant Likely benign rs200350640 GRCh38 Chromosome 1, 226883842: 226883842
42 PSEN2 NM_000447.2(PSEN2): c.279G> C (p.Val93=) single nucleotide variant Likely benign rs200350640 GRCh37 Chromosome 1, 227071543: 227071543
43 PSEN2 NM_000447.2(PSEN2): c.184C> T (p.Arg62Cys) single nucleotide variant Uncertain significance rs150400387 GRCh38 Chromosome 1, 226883747: 226883747
44 PSEN2 NM_000447.2(PSEN2): c.184C> T (p.Arg62Cys) single nucleotide variant Uncertain significance rs150400387 GRCh37 Chromosome 1, 227071448: 227071448
45 PSEN2 NM_000447.2(PSEN2): c.487C> T (p.Arg163Cys) single nucleotide variant Uncertain significance rs200931244 GRCh37 Chromosome 1, 227073369: 227073369
46 PSEN2 NM_000447.2(PSEN2): c.487C> T (p.Arg163Cys) single nucleotide variant Uncertain significance rs200931244 GRCh38 Chromosome 1, 226885668: 226885668

Expression for Alzheimer Disease 4

Search GEO for disease gene expression data for Alzheimer Disease 4.

Pathways for Alzheimer Disease 4

GO Terms for Alzheimer Disease 4

Cellular components related to Alzheimer Disease 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 centrosome GO:0005813 9.33 CDK1 PSEN1 PSEN2
2 cell cortex GO:0005938 9.32 PSEN1 PSEN2
3 kinetochore GO:0000776 9.26 PSEN1 PSEN2
4 integral component of presynaptic membrane GO:0099056 8.96 PSEN1 PSEN2
5 neuronal cell body GO:0043025 8.8 APOE PSEN1 PSEN2

Biological processes related to Alzheimer Disease 4 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of neuron apoptotic process GO:0043524 9.56 APOE PSEN1
2 Notch signaling pathway GO:0007219 9.55 PSEN1 PSEN2
3 cellular calcium ion homeostasis GO:0006874 9.54 APOE PSEN1
4 response to oxidative stress GO:0006979 9.54 APOE GSS PSEN1
5 protein processing GO:0016485 9.52 PSEN1 PSEN2
6 response to cadmium ion GO:0046686 9.51 CDK1 GSS
7 membrane protein ectodomain proteolysis GO:0006509 9.49 PSEN1 PSEN2
8 positive regulation of dendritic spine development GO:0060999 9.48 APOE PSEN1
9 amyloid-beta metabolic process GO:0050435 9.46 PSEN1 PSEN2
10 positive regulation of protein import into nucleus, translocation GO:0033160 9.43 CDK1 PSEN1
11 amyloid precursor protein metabolic process GO:0042982 9.4 APOE PSEN1
12 Notch receptor processing GO:0007220 9.32 PSEN1 PSEN2
13 amyloid precursor protein catabolic process GO:0042987 9.26 PSEN1 PSEN2
14 Notch receptor processing, ligand-dependent GO:0035333 9.16 PSEN1 PSEN2
15 positive regulation of catalytic activity GO:0043085 9.13 APOE PSEN1 PSEN2
16 positive regulation of amyloid fibril formation GO:1905908 8.62 APOE PSEN1

Molecular functions related to Alzheimer Disease 4 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 Alzheimer Disease 4

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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