Recent advances in the genetics of amyotrophic lateral sclerosis and frontotemporal dementia: common pathways in neurodegenerative disease.

Journal article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease classically defined by the impairment of the voluntary motor system and ubiquitin-positive intraneuronal aggregates in anterior horn cells. Frontotemporal dementia (FTD) is a common form of neurodegenerative dementia and presents with personality change associated in a significant subgroup of patients with cortical ubiquitin-only neuropathology (FTD-U). Careful study of ALS as well as FTD patient cohorts suggests clinical as well as pathological overlap of ALS with FTD. The idea that this reflects a shared pathogenesis has received strong support from the identification of new genetic loci on chromosome 9p and of mutations in specific genes (CHMP2B and DCN1) in families with co-segregation of ALS and FTD. The identification of two further genetic causes of FTD-U with (rare) ALS (PGRN) or without ALS (VCP) also provides a starting point for exploring the pathways associated with ubiquitin-mediated protein mishandling in FTD-U and ALS. Pure ALS, through ALS with cognitive impairment and ALS-FTD to pure FTD-U, may represent a continuous spectrum of ubiquitin-associated neurodegenerative disease.

Authors: Talbot, K; Ansorge, O

• Publication status: Published
• Journal: Human molecular genetics
• Volume: 15 Spec No 2
• Issue: SUPPL. 2
• Pages: R182-R187
• Publication date: 2006-10-01
• DOI: 10.1093/hmg/ddl202
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Ubiquitin; Amyotrophic Lateral Sclerosis; Endosomal Sorting Complexes Required for Transport; Cell Cycle Proteins; Nerve Tissue Proteins; Adenosine Triphosphatases; Intercellular Signaling Peptides and Proteins; Dementia; Inclusion Bodies; Humans; Microtubule-Associated Proteins; Nerve Degeneration; Genetic Linkage