Details of Disease

General Information of Disease (ID: DISA7775)

• Disease Name: Semantic dementia
• Synonyms: Ftld with Tau inclusions; multiple system tauopathy with presenile dementia; dementia, frontotemporal, with Parkinsonism; FTD; Wilhelmsen-Lynch disease; Ftdp17; disinhibition-dementia-Parkinsonism-amyotrophy Complex; frontotemporal lobe dementia; frontotemporal lobar Degeneration with Tau inclusions; frontotemporal dementia; frontotemporal dementia with Parkinsonism; Pick Complex; Pallidopontonigral Degeneration; semantic variant PPA; dementia, frontotemporal, with or without parkinsonism; semantic primary progressive aphasia; dementia, frontotemporal
• Definition: Semantic dementia (SD) is a form of frontotemporal dementia (FTD), characterized by the progressive, amodal and profound loss of semantic knowledge (combination of visual associative agnosia, anomia, surface dyslexia or dysgraphia and disrupted comprehension of word meaning) and behavioral abnormalities, attributable to the degeneration of the anterior temporal lobes.
• Disease Hierarchy:
  DIS9HZET: Progressive non-fluent aphasia
  DISQHX2V: Behavioral variant of frontotemporal dementia
  DISA7775: Semantic dementia
• Disease Identifiers:
  MONDO ID: MONDO_0010857
  MESH ID: D057180
  UMLS CUI: C0338462
  MedGen ID: 83268
  HPO ID: HP:0030219
  Orphanet ID: 100069
  SNOMED CT ID: 230288001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
C9orf72	TTA4SHR	Strong	Biomarker	[1]
GRN	TT0LWE3	Strong	Altered Expression	[2]
MAPT	TTXZCO0	Strong	Autosomal dominant	[3]
MAPT	TTS87KH	Strong	Genetic Variation	[1]
PSEN1	TTZ3S8C	Strong	Autosomal dominant	[3]
PSEN1	TTZ3S8C	Strong	GermlineCausalMutation	[4]
TARDBP	TT9RZ03	Strong	Genetic Variation	[5]
TREM2	TTQRMSJ	Strong	SusceptibilityMutation	[6]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TMEM106B	OTUWA6NW	moderate	SusceptibilityMutation	[7]
CHMP2B	OTZA7RJB	Strong	SusceptibilityMutation	[8]
MAPT	OTMTP2Z7	Strong	Autosomal dominant	[3]
PCBP2	OTXCN9CG	Strong	Biomarker	[9]
PSEN1	OTKL39RT	Strong	Autosomal dominant	[3]

References

• [1] Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype.Brain Pathol. 2017 Nov;27(6):723-736. doi: 10.1111/bpa.12486. Epub 2017 Mar 2.
• [2] CSF Biomarkers of Neurodegeneration in Progressive Non-fluent Aphasia and Other Forms of Frontotemporal Dementia: Clues for Pathomechanisms?.Front Neurol. 2018 Jul 2;9:504. doi: 10.3389/fneur.2018.00504. eCollection 2018.
• [3] 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.
• [4] Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology. 2000 Nov 28;55(10):1577-8. doi: 10.1212/wnl.55.10.1577.
• [5] [(18)F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia.J Neurol Neurosurg Psychiatry. 2018 Oct;89(10):1032-1037. doi: 10.1136/jnnp-2017-316402. Epub 2017 Sep 14.
• [6] Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes.Neurobiol Aging. 2014 Nov;35(11):2657.e13-2657.e19. doi: 10.1016/j.neurobiolaging.2014.06.018. Epub 2014 Jun 20.
• [7] What we know about TMEM106B in neurodegeneration.Acta Neuropathol. 2016 Nov;132(5):639-651. doi: 10.1007/s00401-016-1610-9. Epub 2016 Aug 20.
• [8] Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review.Transl Neurodegener. 2013 Apr 19;2(1):8. doi: 10.1186/2047-9158-2-8.
• [9] Heterogeneous ribonuclear protein E2 (hnRNP E2) is associated with TDP-43-immunoreactive neurites in Semantic Dementia but not with other TDP-43 pathological subtypes of Frontotemporal Lobar Degeneration.Acta Neuropathol Commun. 2017 Jun 30;5(1):54. doi: 10.1186/s40478-017-0454-4.