MCID: ALZ054
MIFTS: 41

Alzheimer Disease 4

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Mental 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 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Neuroscience. The drugs Miconazole and Benzocaine have been mentioned in the context of this disorder. Related phenotypes are dementia and sleep-wake cycle disturbance

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
Early-Onset Familial Alzheimer Disease Alzheimer Disease Type 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 24)
# Related Disease Score Top Affiliating Genes
1 early-onset, autosomal dominant alzheimer disease 30.9 PSEN1 PSEN2
2 tardive dyskinesia 10.0
3 alexia 9.7 APOE PSEN1
4 gait apraxia 9.7 APOE PSEN1
5 semantic dementia 9.7 APOE PSEN1
6 cerebral amyloid angiopathy, cst3-related 9.6 APOE PSEN1
7 aphasia 9.6 APOE PSEN1
8 pick disease of brain 9.6 APOE PSEN1
9 visual agnosia 9.6 PSEN1 PSEN2
10 supranuclear palsy, progressive, 1 9.6 APOE PSEN1
11 early-onset familial alzheimer disease 9.5 PSEN1 PSEN2
12 familial isolated dilated cardiomyopathy 9.5 PSEN1 PSEN2
13 vascular dementia 9.5 APOE PSEN1
14 dementia, lewy body 9.5 APOE PSEN1
15 speech and communication disorders 9.4 APOE PSEN1
16 disease of mental health 9.3 APOE PSEN1
17 familial idiopathic basal ganglia calcification 9.0 APOE PSEN1 PSEN2
18 alzheimer disease 2 9.0 APOE PSEN1 PSEN2
19 central nervous system disease 9.0 APOE PSEN1 PSEN2
20 nervous system disease 9.0 APOE PSEN1 PSEN2
21 frontotemporal dementia 9.0 APOE PSEN1 PSEN2
22 dementia 9.0 APOE PSEN1 PSEN2
23 amyloidosis 9.0 APOE PSEN1
24 alzheimer disease 8.5 APOE PSEN1 PSEN2

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:
presenile dementia
sleep-wake cycle disturbance

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 sleep-wake cycle disturbance 32 HP:0006979
3 alzheimer disease 32 HP:0002511
4 cerebral amyloid angiopathy 32 HP:0011970

MGI Mouse Phenotypes related to Alzheimer Disease 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.5 APOE PSEN1 PSEN2
2 limbs/digits/tail MP:0005371 9.43 APOE PSEN1 PSEN2
3 renal/urinary system MP:0005367 9.33 APOE PSEN1 PSEN2
4 respiratory system MP:0005388 9.13 APOE PSEN1 PSEN2
5 vision/eye MP:0005391 8.8 APOE PSEN1 PSEN2

Drugs & Therapeutics for Alzheimer Disease 4

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

(show all 16)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miconazole Approved, Investigational, Vet_approved Phase 3 22916-47-8 4189
2
Benzocaine Approved, Investigational Phase 3 1994-09-7, 94-09-7 2337
3 tannic acid Approved, Nutraceutical Phase 3
4 Cyclosporins Phase 3
5 Dermatologic Agents Phase 3
6 Immunosuppressive Agents Phase 3
7 Anti-Infective Agents Phase 3
8 Antifungal Agents Phase 3
9 Antirheumatic Agents Phase 3
10 Calcineurin Inhibitors Phase 3
11
Aluminum hydroxide Approved, Investigational Phase 1 21645-51-2
12 Vaccines Phase 1
13 Monophosphoryl lipid A Phase 1
14 Antibodies Phase 1
15 Immunoglobulins Phase 1
16 Krestin Phase 1

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 Experimental AD4-H5-VTN Vaccine in Healthy Volunteers Completed NCT01443936 Phase 1
4 Safety and Immunogenicity of Replication-Competent Adenovirus 4-vectored Vaccine for Avian Influenza H5N1 Completed NCT01006798 Phase 1
5 A Phase 1 Ascending Dose Study to Assess the Safety and Immunogenicity of Adenovirus Anthrax Vector Candidate Vaccines Completed NCT01979406 Phase 1
6 Clinical Trial of HIV Vaccine Combinations in Healthy Men and Women Recruiting NCT03408262 Phase 1
7 Study of Safety and Immunogenicity of HIV Vaccines in Healthy Volunteers Active, not recruiting NCT01989533 Phase 1
8 Study to Evaluate the Safety and Immunogenicity of Orally-administered HIV Vaccine in Healthy, HIV-uninfected Adult Participants Active, not recruiting NCT02771730 Phase 1
9 A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047 Terminated NCT03160339 Phase 1

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

Publications for Alzheimer Disease 4

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 36)
# 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.1289C> T (p.Thr430Met) single nucleotide variant Pathogenic rs63750666 GRCh37 Chromosome 1, 227083222: 227083222
6 PSEN2 NM_000447.2(PSEN2): c.1289C> T (p.Thr430Met) single nucleotide variant Pathogenic rs63750666 GRCh38 Chromosome 1, 226895521: 226895521
7 PSEN2 NM_000447.2(PSEN2): c.364A> C (p.Thr122Pro) single nucleotide variant Likely pathogenic rs63749851 GRCh37 Chromosome 1, 227073246: 227073246
8 PSEN2 NM_000447.2(PSEN2): c.364A> C (p.Thr122Pro) single nucleotide variant Likely pathogenic rs63749851 GRCh38 Chromosome 1, 226885545: 226885545
9 PSEN2 NM_000447.2(PSEN2): c.717G> A (p.Met239Ile) single nucleotide variant Pathogenic rs63749884 GRCh37 Chromosome 1, 227076680: 227076680
10 PSEN2 NM_000447.2(PSEN2): c.717G> A (p.Met239Ile) single nucleotide variant Pathogenic rs63749884 GRCh38 Chromosome 1, 226888979: 226888979
11 PSEN2 NM_000447.2(PSEN2): c.365C> G (p.Thr122Arg) single nucleotide variant Pathogenic rs28936380 GRCh37 Chromosome 1, 227073247: 227073247
12 PSEN2 NM_000447.2(PSEN2): c.365C> G (p.Thr122Arg) single nucleotide variant Pathogenic rs28936380 GRCh38 Chromosome 1, 226885546: 226885546
13 PSEN2 NM_000447.2(PSEN2): c.254C> T (p.Ala85Val) single nucleotide variant Pathogenic rs63750048 GRCh37 Chromosome 1, 227071518: 227071518
14 PSEN2 NM_000447.2(PSEN2): c.254C> T (p.Ala85Val) single nucleotide variant Pathogenic rs63750048 GRCh38 Chromosome 1, 226883817: 226883817
15 PSEN1 NG_007386.2: g.73292_77847del4556 deletion Pathogenic GRCh37 Chromosome 14, 73671470: 73676025
16 PSEN1 NG_007386.2: g.73292_77847del4556 deletion Pathogenic GRCh38 Chromosome 14, 73204762: 73209317
17 PSEN1 NM_000021.3(PSEN1): c.806G> A (p.Arg269His) single nucleotide variant Pathogenic rs63750900 GRCh37 Chromosome 14, 73664775: 73664775
18 PSEN1 NM_000021.3(PSEN1): c.806G> A (p.Arg269His) single nucleotide variant Pathogenic rs63750900 GRCh38 Chromosome 14, 73198067: 73198067
19 PSEN2 NM_000447.2(PSEN2): c.129C> T (p.Asn43=) single nucleotide variant Benign/Likely benign rs6759 GRCh38 Chromosome 1, 226882036: 226882036
20 PSEN2 NM_000447.2(PSEN2): c.129C> T (p.Asn43=) single nucleotide variant Benign/Likely benign rs6759 GRCh37 Chromosome 1, 227069737: 227069737
21 PSEN2 NM_000447.2(PSEN2): c.261C> T (p.His87=) single nucleotide variant Benign/Likely benign rs1046240 GRCh38 Chromosome 1, 226883824: 226883824
22 PSEN2 NM_000447.2(PSEN2): c.261C> T (p.His87=) single nucleotide variant Benign/Likely benign rs1046240 GRCh37 Chromosome 1, 227071525: 227071525
23 PSEN2 NM_000447.2(PSEN2): c.903G> T (p.Thr301=) single nucleotide variant Benign/Likely benign rs6426553 GRCh38 Chromosome 1, 226891294: 226891294
24 PSEN2 NM_000447.2(PSEN2): c.903G> T (p.Thr301=) single nucleotide variant Benign/Likely benign rs6426553 GRCh37 Chromosome 1, 227078995: 227078995
25 PSEN2 NM_000447.2(PSEN2): c.886+2_886+4delTGA deletion Likely pathogenic GRCh37 Chromosome 1, 227077836: 227077838
26 PSEN2 NM_000447.2(PSEN2): c.886+2_886+4delTGA deletion Likely pathogenic GRCh38 Chromosome 1, 226890135: 226890137
27 PSEN2 NC_000001.11: g.(?_226881888)_(226895599_?)del deletion Pathogenic GRCh38 Chromosome 1, 226881888: 226895599
28 PSEN2 NC_000001.11: g.(?_226881888)_(226895599_?)del deletion Pathogenic GRCh37 Chromosome 1, 227069589: 227083300
29 PSEN2 NM_000447.2(PSEN2): c.132T> A (p.Thr44=) single nucleotide variant Benign rs143227762 GRCh38 Chromosome 1, 226882039: 226882039
30 PSEN2 NM_000447.2(PSEN2): c.132T> A (p.Thr44=) single nucleotide variant Benign rs143227762 GRCh37 Chromosome 1, 227069740: 227069740
31 PSEN2 NM_000447.2(PSEN2): c.1176C> T (p.Phe392=) single nucleotide variant Benign rs115652716 GRCh37 Chromosome 1, 227081811: 227081811
32 PSEN2 NM_000447.2(PSEN2): c.1176C> T (p.Phe392=) single nucleotide variant Benign rs115652716 GRCh38 Chromosome 1, 226894110: 226894110
33 PSEN2 NM_000447.2(PSEN2): c.423C> T (p.Asn141=) single nucleotide variant Benign rs116003409 GRCh38 Chromosome 1, 226885604: 226885604
34 PSEN2 NM_000447.2(PSEN2): c.423C> T (p.Asn141=) single nucleotide variant Benign rs116003409 GRCh37 Chromosome 1, 227073305: 227073305
35 PSEN2 NM_000447.2(PSEN2): c.279G> C (p.Val93=) single nucleotide variant Likely benign rs200350640 GRCh37 Chromosome 1, 227071543: 227071543
36 PSEN2 NM_000447.2(PSEN2): c.279G> C (p.Val93=) single nucleotide variant Likely benign rs200350640 GRCh38 Chromosome 1, 226883842: 226883842

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:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.65 APOE PSEN1 PSEN2
2 Golgi apparatus GO:0005794 9.63 APOE PSEN1 PSEN2
3 membrane raft GO:0045121 9.49 PSEN1 PSEN2
4 cell cortex GO:0005938 9.43 PSEN1 PSEN2
5 kinetochore GO:0000776 9.4 PSEN1 PSEN2
6 growth cone GO:0030426 9.37 PSEN1 PSEN2
7 Z disc GO:0030018 9.32 PSEN1 PSEN2
8 neuromuscular junction GO:0031594 9.26 PSEN1 PSEN2
9 dendritic shaft GO:0043198 9.16 PSEN1 PSEN2
10 neuronal cell body GO:0043025 9.13 APOE PSEN1 PSEN2
11 ciliary rootlet GO:0035253 8.62 PSEN1 PSEN2

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 cellular protein metabolic process GO:0044267 9.58 APOE PSEN1
2 calcium ion transport GO:0006816 9.57 PSEN1 PSEN2
3 negative regulation of neuron apoptotic process GO:0043524 9.56 APOE PSEN1
4 response to oxidative stress GO:0006979 9.55 APOE PSEN1
5 Notch signaling pathway GO:0007219 9.54 PSEN1 PSEN2
6 cellular calcium ion homeostasis GO:0006874 9.52 APOE PSEN1
7 ephrin receptor signaling pathway GO:0048013 9.51 PSEN1 PSEN2
8 protein processing GO:0016485 9.49 PSEN1 PSEN2
9 positive regulation of dendritic spine development GO:0060999 9.48 APOE PSEN1
10 membrane protein ectodomain proteolysis GO:0006509 9.46 PSEN1 PSEN2
11 membrane protein intracellular domain proteolysis GO:0031293 9.43 PSEN1 PSEN2
12 Notch receptor processing GO:0007220 9.4 PSEN1 PSEN2
13 amyloid-beta metabolic process GO:0050435 9.37 PSEN1 PSEN2
14 Notch receptor processing, ligand-dependent GO:0035333 9.32 PSEN1 PSEN2
15 amyloid precursor protein metabolic process GO:0042982 9.26 APOE PSEN1
16 amyloid precursor protein catabolic process GO:0042987 9.16 PSEN1 PSEN2
17 positive regulation of amyloid fibril formation GO:1905908 8.96 APOE PSEN1
18 positive regulation of catalytic activity GO:0043085 8.8 APOE PSEN1 PSEN2

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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