Details of Disease

Disease Name

Alzheimer disease 3

Alzheimer disease, familial, 3; Alzheimer disease early onset type 3; AD; Alzheimer disease 3, early-onset; Alzheimer disease, familial, 3, with spastic paraparesis and apraxia; Alzheimer disease, familial, 3, with spastic paraparesis and unusual plaques; Alzheimer disease type 3; Alzheimer disease, type 3; Alzheimer disease, protection against, due to APOE3-Christchurch; AD3; Alzheimer's disease 3; familial Alzheimer disease, type 3; Alzheimer disease 3, early onset; Alzheimer disease, type 3, with spastic paraparesis and unusual plaques; PSEN1 early-onset autosomal dominant Alzheimer disease; early-onset autosomal dominant Alzheimer disease caused by mutation in PSEN1; Alzheimer's disease type 3; Alzheimer disease 3; Alzheimer disease familial 3; familial Alzheimer's disease, type 3; Alzheimer disease, type 3, with spastic paraparesis and apraxia

Definition

Alzheimer's disease with an early onset (starts before the age of 65). It is caused by mutations in the PSEN1 gene.

Disease Hierarchy

DISFAUJO: Early-onset autosomal dominant Alzheimer disease

DISVT69G: Alzheimer disease 3

Disease Identifiers

MONDO ID

MONDO_0011913

MESH ID

C536598

UMLS CUI

C1843013

OMIM ID

607822

MedGen ID

334304

General Information of Disease (ID: DISVT69G)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
APP	TTE4KHA	Limited	Genetic Variation	[1]
BACE1	TTJUNZF	Limited	Biomarker	[2]
PSEN2	TTWN3F4	Limited	Genetic Variation	[3]
CHAT	TTKYFSB	Strong	Altered Expression	[4]
IDE	TT2EDHU	Strong	Genetic Variation	[5]
IL31	TT1RJXK	Strong	Altered Expression	[6]
LIPA	TTS8T1M	Strong	Genetic Variation	[7]
PSEN1	TTZ3S8C	Strong	Autosomal dominant	[8]
SGO1	TTBPKGD	Strong	Biomarker	[9]
SNCA	TT08OSU	Strong	Biomarker	[10]
TREM2	TTQRMSJ	Strong	Biomarker	[11]
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⏷ Show the Full List of 11 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MARS1	DE0K52I	Strong	Genetic Variation	[12]
NMNAT2	DE2HB58	Strong	Altered Expression	[13]
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This Disease Is Related to 39 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NLRP12	OTGR132Z	Limited	Biomarker	[14]
ANKK1	OT0OM1O0	Strong	Genetic Variation	[15]
APLP2	OTTFE53M	Strong	Biomarker	[16]
APOD	OTT77XW8	Strong	Altered Expression	[17]
CCL26	OT2B7HR9	Strong	Biomarker	[18]
CFDP1	OTXY7J96	Strong	Altered Expression	[19]
CHD1	OT9R9G0H	Strong	Biomarker	[20]
COL3A1	OTT1EMLM	Strong	Biomarker	[21]
COTL1	OT6YCNLF	Strong	Biomarker	[22]
CUL4A	OTTBV70J	Strong	Biomarker	[23]
DAB1	OTPL9MA3	Strong	Altered Expression	[24]
DEFA1	OT5N1B9B	Strong	Altered Expression	[25]
DEFB104A	OTLQZR6K	Strong	Genetic Variation	[25]
DOCK8	OTNQLL21	Strong	Biomarker	[26]
ECSCR	OT9L72MD	Strong	Altered Expression	[27]
EIF4G2	OTEO98CR	Strong	Altered Expression	[19]
FLG	OTE9QDV6	Strong	Genetic Variation	[28]
GDF7	OTNZY74B	Strong	Biomarker	[29]
IL9R	OTILCLXA	Strong	Altered Expression	[30]
KALRN	OT8WRCBH	Strong	Altered Expression	[31]
KIF21B	OTFXFIU3	Strong	Biomarker	[32]
KPRP	OTRJF3OY	Strong	Altered Expression	[33]
OTOF	OTXQMJY8	Strong	Genetic Variation	[34]
PHF13	OT89FV4A	Strong	Biomarker	[35]
PICALM	OTQVRPMQ	Strong	Biomarker	[36]
PLXNA3	OTMZIBVG	Strong	Biomarker	[37]
PSEN1	OTKL39RT	Strong	Autosomal dominant	[8]
PSMD2	OT6HZHN7	Strong	Altered Expression	[19]
RAD23B	OT0PGOG3	Strong	Biomarker	[38]
SAA2	OTYAVJWG	Strong	Altered Expression	[39]
SAMD4A	OT4MKCC8	Strong	Biomarker	[40]
SBSN	OT89RKJH	Strong	Biomarker	[41]
SLA2	OTNVE666	Strong	Genetic Variation	[12]
SNRPG	OTWX4XK1	Strong	Biomarker	[40]
SPAST	OTIF3AJI	Strong	Genetic Variation	[42]
SUCLA2	OTMZD4PW	Strong	Biomarker	[43]
TBC1D8	OT2011SS	Strong	Biomarker	[44]
TBX2	OTTOT7A9	Strong	Altered Expression	[45]
TSPAN3	OT7WS6ZI	Strong	Altered Expression	[46]
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⏷ Show the Full List of 39 DOT(s)

References

1	Generation of induced pluripotent stem cells (iPSCs) IRMBi002-A from an Alzheimer's disease patient carrying a D694N mutation in the APP gene.Stem Cell Res. 2019 May;37:101438. doi: 10.1016/j.scr.2019.101438. Epub 2019 Apr 15.
2	Methylation analysis of multiple genes in blood DNA of Alzheimer's disease and healthy individuals.Neurosci Lett. 2015 Jul 23;600:143-7. doi: 10.1016/j.neulet.2015.06.009. Epub 2015 Jun 12.
3	A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer's disease.Clin Interv Aging. 2018 Jul 31;13:1321-1329. doi: 10.2147/CIA.S170374. eCollection 2018.
4	Cholinergic dysfunction in diseases with Lewy bodies.Neurology. 2000 Jan 25;54(2):407-11. doi: 10.1212/wnl.54.2.407.
5	Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease.Hum Mutat. 2004 Apr;23(4):334-42. doi: 10.1002/humu.20016.
6	Assessment of IL-31 levels and disease severity in children with atopic dermatitis.Allergol Immunopathol (Madr). 2018 Jul-Aug;46(4):322-325. doi: 10.1016/j.aller.2017.10.005. Epub 2018 Mar 17.
7	Influence of lysosomal acid lipase polymorphisms on chromosome 10 on the risk of Alzheimer's disease and cholesterol metabolism.Neurosci Lett. 2006 Jul 24;402(3):262-6. doi: 10.1016/j.neulet.2006.04.009. Epub 2006 May 26.
8	The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
9	Spontaneous development of Alzheimer's disease-associated brain pathology in a Shugoshin-1 mouse cohesinopathy model.Aging Cell. 2018 Aug;17(4):e12797. doi: 10.1111/acel.12797. Epub 2018 Jun 25.
10	Acetylation as a major determinant to microtubule-dependent autophagy: Relevance to Alzheimer's and Parkinson disease pathology.Biochim Biophys Acta Mol Basis Dis. 2019 Aug 1;1865(8):2008-2023. doi: 10.1016/j.bbadis.2018.11.014. Epub 2018 Dec 17.
11	Role of TREM2 in Alzheimer's Disease and its Consequences on - Amyloid, Tau and Neurofibrillary Tangles.Curr Alzheimer Res. 2019;16(13):1216-1229. doi: 10.2174/1567205016666190903102822.
12	Histopathological features of a patient with Charcot-Marie-Tooth disease type 2U/AD-CMTax-MARS.J Peripher Nerv Syst. 2016 Dec;21(4):370-374. doi: 10.1111/jns.12193.
13	NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies.PLoS Biol. 2016 Jun 2;14(6):e1002472. doi: 10.1371/journal.pbio.1002472. eCollection 2016 Jun.
14	NLRP12 autoinflammatory disease: a Chinese case series and literature review.Clin Rheumatol. 2017 Jul;36(7):1661-1667. doi: 10.1007/s10067-016-3410-y. Epub 2016 Sep 16.
15	The association of DRD2 -141C and ANKK1 TaqIA polymorphisms with alcohol dependence in Korean population classified by the Lesch typology.Alcohol Alcohol. 2013 Jul-Aug;48(4):426-32. doi: 10.1093/alcalc/agt029. Epub 2013 Apr 4.
16	Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression.Cell Death Differ. 2007 Jan;14(1):79-91. doi: 10.1038/sj.cdd.4401928. Epub 2006 Apr 28.
17	Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in African-Americans.Am J Med Genet B Neuropsychiatr Genet. 2003 Jan 1;116B(1):98-101. doi: 10.1002/ajmg.b.10798.
18	Analysis of eotaxin 1/CCL11, eotaxin 2/CCL24 and eotaxin 3/CCL26 expression in lesional and non-lesional skin of patients with atopic dermatitis.Cytokine. 2010 May;50(2):181-5. doi: 10.1016/j.cyto.2010.02.016. Epub 2010 Mar 16.
19	Melanotransferrin is produced by senile plaque-associated reactive microglia in Alzheimer's disease.Brain Res. 1999 Oct 16;845(1):1-5. doi: 10.1016/s0006-8993(99)01767-9.
20	Computational identification of key genes that may regulate gene expression reprogramming in Alzheimer's patients.PLoS One. 2019 Sep 23;14(9):e0222921. doi: 10.1371/journal.pone.0222921. eCollection 2019.
21	Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency.Eur J Hum Genet. 2010 Dec;18(12):1315-21. doi: 10.1038/ejhg.2010.105. Epub 2010 Jul 21.
22	Quantitative proteomics of acutely-isolated mouse microglia identifies novel immune Alzheimer's disease-related proteins.Mol Neurodegener. 2018 Jun 28;13(1):34. doi: 10.1186/s13024-018-0266-4.
23	A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing.J Virol. 2019 Jan 4;93(2):e01265-18. doi: 10.1128/JVI.01265-18. Print 2019 Jan 15.
24	The AICD interacting protein DAB1 is up-regulated in Alzheimer frontal cortex brain samples and causes deregulation of proteins involved in gene expression changes. Curr Alzheimer Res. 2011 Aug;8(5):573-82.
25	Relevance of defensin -2 and defensins (HNP1-3) in Alzheimer's disease.Psychiatry Res. 2016 May 30;239:342-5. doi: 10.1016/j.psychres.2016.03.045. Epub 2016 Mar 31.
26	Quantitative profiling of cytokines and chemokines in DOCK8-deficient and atopic dermatitis patients.Allergy. 2019 Feb;74(2):370-379. doi: 10.1111/all.13610. Epub 2018 Oct 15.
27	Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-APPswe Mice Without Inducing Microhemorrhage.J Alzheimers Dis. 2017;59(4):1393-1413. doi: 10.3233/JAD-170056.
28	The Value of FLG Null Mutations in Predicting Treatment Response in Atopic Dermatitis: An Observational Study in Finnish Patients.Acta Derm Venereol. 2017 Apr 6;97(4):456-463. doi: 10.2340/00015555-2578.
29	Synergistic promoting effects of bone morphogenetic protein 12/connective tissue growth factor on functional differentiation of tendon derived stem cells and patellar tendon window defect regeneration.J Biomech. 2018 Jan 3;66:95-102. doi: 10.1016/j.jbiomech.2017.11.004. Epub 2017 Nov 7.
30	IL-9 induces VEGF secretion from human mast cells and IL-9/IL-9 receptor genes are overexpressed in atopic dermatitis.PLoS One. 2012;7(3):e33271. doi: 10.1371/journal.pone.0033271. Epub 2012 Mar 8.
31	Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer's disease hippocampus.J Alzheimers Dis. 2007 Nov;12(3):271-81. doi: 10.3233/jad-2007-12309.
32	Abundant kif21b is associated with accelerated progression in neurodegenerative diseases.Acta Neuropathol Commun. 2014 Oct 3;2:144. doi: 10.1186/s40478-014-0144-4.
33	Keratinocyte Proline-Rich Protein DeficiencyinAtopic Dermatitis Leads to Barrier Disruption.J Invest Dermatol. 2019 Sep;139(9):1867-1875.e7. doi: 10.1016/j.jid.2019.02.030. Epub 2019 Mar 21.
34	Identification of a novel splice site variant of OTOF in the Korean nonsyndromic hearing loss population with low prevalence of the OTOF mutations.Int J Pediatr Otorhinolaryngol. 2014 Jul;78(7):1030-5. doi: 10.1016/j.ijporl.2014.03.033. Epub 2014 Apr 24.
35	SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection.PLoS Pathog. 2013;9(11):e1003775. doi: 10.1371/journal.ppat.1003775. Epub 2013 Nov 21.
36	Genetic association of PICALM polymorphisms with Alzheimer's disease in Han Chinese.J Neurol Sci. 2011 Jan 15;300(1-2):78-80. doi: 10.1016/j.jns.2010.09.027. Epub 2010 Oct 15.
37	White matter architecture in major depression with anxious distress symptoms.Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30;94:109664. doi: 10.1016/j.pnpbp.2019.109664. Epub 2019 May 31.
38	The DNA repair-ubiquitin-associated HR23 proteins are constituents of neuronal inclusions in specific neurodegenerative disorders without hampering DNA repair.Neurobiol Dis. 2006 Sep;23(3):708-16. doi: 10.1016/j.nbd.2006.06.005. Epub 2006 Jul 24.
39	Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis.PLoS One. 2017 Jul 14;12(7):e0181486. doi: 10.1371/journal.pone.0181486. eCollection 2017.
40	Functional segregation of executive control network and frontoparietal network in Alzheimer's disease.Cortex. 2019 Nov;120:36-48. doi: 10.1016/j.cortex.2019.04.026. Epub 2019 May 18.
41	Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis.J Dermatol Sci. 2019 Sep;95(3):107-112. doi: 10.1016/j.jdermsci.2019.07.009. Epub 2019 Jul 27.
42	Novel SPAST deletion and reduced DPY30 expression in a Spastic Paraplegia type 4 kindred.BMC Med Genet. 2014 Apr 1;15:39. doi: 10.1186/1471-2350-15-39.
43	Curcumin-Loaded Nanocapsules Reverses the Depressant-Like Behavior and Oxidative Stress Induced by -Amyloid in Mice.Neuroscience. 2019 Dec 15;423:122-130. doi: 10.1016/j.neuroscience.2019.09.032. Epub 2019 Nov 4.
44	Adenoviral gene therapy for renal cancer requires retargeting to alternative cellular receptors.Cancer Res. 2002 Aug 1;62(15):4273-81.
45	Transcriptional repression of the ectodomain sheddase ADAM10 by TBX2 and potential implication for Alzheimer's disease.Cell Mol Life Sci. 2019 Mar;76(5):1005-1025. doi: 10.1007/s00018-018-2998-2. Epub 2019 Jan 1.
46	Tetraspanin 3: A central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein.Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):217-230. doi: 10.1016/j.bbamcr.2016.11.003. Epub 2016 Nov 3.