Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion

Background: TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables. Methods: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, Aβ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. Results: There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). Conclusion: CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.

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C9ORF72 expansion in amyotrophic lateral sclerosis/frontotemporal dementia also causes parkinsonism

Movement Disorders ◽

10.1002/mds.25022 ◽

2012 ◽

Vol 27 (8) ◽

pp. 1072-1074 ◽

Cited By ~ 31

Author(s):

Seán O'Dowd ◽

Denis Curtin ◽

Adrian J. Waite ◽

Kinley Roberts ◽

Niall Pender ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Frontotemporal Dementia ◽

C9orf72 Expansion ◽

Lateral Sclerosis

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Amyotrophic Lateral Sclerosis–Frontotemporal Lobar Dementia in 3 Families With p.Ala382Thr TARDBP Mutations

Archives of Neurology ◽

10.1001/archneurol.2010.173 ◽

2010 ◽

Vol 67 (8) ◽

Cited By ~ 44

Author(s):

Adriano Chiò ◽

Andrea Calvo ◽

Cristina Moglia ◽

Gabriella Restagno ◽

Irene Ossola ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Frontotemporal Lobar Dementia ◽

Lateral Sclerosis

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P4-235: TDP-43 OLIGOMER PATHOLOGY IN FRONTOTEMPORAL LOBAR DEMENTIA, AMYOTROPHIC LATERAL SCLEROSIS AND ALZHEIMER'S DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.07.056 ◽

2006 ◽

Vol 14 (7S_Part_29) ◽

pp. P1532-P1533

Author(s):

Wei-Wei Chang ◽

Yu-Sheng Fang ◽

Yao-Hsiang Shih ◽

Shih-Han Huang ◽

Yun-Ru Ruby Chen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyotrophic Lateral Sclerosis ◽

Frontotemporal Lobar Dementia ◽

Lateral Sclerosis

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C9orf72 expansion within astrocytes reduces metabolic flexibility in amyotrophic lateral sclerosis

Brain ◽

10.1093/brain/awz302 ◽

2019 ◽

Vol 142 (12) ◽

pp. 3771-3790 ◽

Cited By ~ 16

Author(s):

Scott P Allen ◽

Benjamin Hall ◽

Ryan Woof ◽

Laura Francis ◽

Noemi Gatto ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Energy Metabolism ◽

Animal Models ◽

Metabolic Profiling ◽

Metabolic Flexibility ◽

Substrate Transport ◽

Energy Substrate ◽

C9orf72 Expansion ◽

Lateral Sclerosis

Energy metabolism is altered in amyotrophic lateral sclerosis and its animal models. Using metabolic profiling, Allen et al. reveal a loss of metabolic flexibility in induced astrocytes derived from patients with C9orf72 ALS, caused by defects in glycogen, fructose and mitochondrial energy substrate transport.

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Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Patients with Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis with the C9ORF72 Repeat Expansion

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000371704 ◽

2015 ◽

Vol 39 (5-6) ◽

pp. 287-293 ◽

Cited By ~ 8

Author(s):

Anna Kämäläinen ◽

Sanna-Kaisa Herukka ◽

Päivi Hartikainen ◽

Seppo Helisalmi ◽

Virpi Moilanen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyotrophic Lateral Sclerosis ◽

Cerebrospinal Fluid ◽

Frontotemporal Lobar Degeneration ◽

Clinical Signs ◽

Clinical Diagnostics ◽

C9orf72 Expansion ◽

T Tau ◽

Lateral Sclerosis

Background: The C9ORF72 expansion is one of the most common causes of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The C9ORF72 expansion is associated with TDP-43 and p62 neuropathology, and amyloid plaques and neurofibrillary tangles are not common in patients with the C9ORF72 expansion. Therefore, we hypothesized that cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease [AD; Aβ1-42, total tau (T-tau) and phospho-tau] are normal in these patients. Methods: The CSF Aβ1-42, T-tau and phospho-tau levels were measured in 40 Finnish patients with the C9ORF72 expansion (29 FTLD, 10 ALS and 1 FTLD-ALS) using ELISA. Results: A decreased Aβ1-42 level was found in 25% of cases, while there were only single cases with changes in the t-Tau or phospho-tau level. The patients with abnormal biomarkers fulfilled the clinical criteria of the behavioral variant frontotemporal dementia and expressed no clinical signs of AD. Conclusions: In clinical diagnostics, a decreased CSF Aβ1-42 level does not exclude the C9ORF72 expansion associated with FTLD.

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