C9orf72 G4C2 repeat expansions in Alzheimer's disease and mild cognitive impairment

Cacace, Rita; Cauwenberghe, Caroline Van; Bettens, Karolien; Gijselinck, Ilse; Zee, Julie van der; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; Dongen, Jasper Van; Bäumer, Veerle; Dillen, Lubina; Mattheijssens, Maria; Peeters, Karin; Cruts, Marc; Vandenberghe, Rik; Deyn, Peter Paul De; Broeckhoven, Christine Van; Sleegers, Kristel

doi:10.1016/j.neurobiolaging.2012.12.019

Cited by 70 publications

(50 citation statements)

References 33 publications

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“…Mutations have been identified, at low frequencies (less than 1%-2%), in genes causing frontotemporal lobar degeneration (FTLD), that is, mutations in MAPT [83,84] and in granulin (GRN) [80][81][82], and the repeat expansion in C9orf72 [85][86][87] (Table 3). The genetic heterogeneity of the phenotypic presentation of AD supports that both diseases form part of an AD-FTLD disease continuum [100,101].…”

Section: The Role Of Other Neurodegenerative Brain Diseases Genes In mentioning

confidence: 99%

Molecular genetics of early‐onset Alzheimer's disease revisited

Cacace

Sleegers

Broeckhoven

2016

Alzheimer's & Dementia

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442

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As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries.

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Section: The Role Of Other Neurodegenerative Brain Diseases Genes In mentioning

confidence: 99%

Molecular genetics of early‐onset Alzheimer's disease revisited

Cacace

Sleegers

Broeckhoven

2016

Alzheimer's & Dementia

Self Cite

442

404

View full text Add to dashboard Cite

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“…Since FTLD is a neuropathologically heterogeneous syndrome, it has been difficult to find sensitive and specific biomarkers that are accurate enough to determine different neuropathological groups. For example, a major problem with CSF biomarker concentrations has been the overlap of FTLD with AD or control groups [12,13,14,15,16]. …”

Section: Introductionmentioning

confidence: 99%

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

Kämäläinen

Herukka

Hartikainen

et al. 2015

Dement Geriatr Cogn Disord

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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; Aβ_1-42, total tau (T-tau) and phospho-tau] are normal in these patients. Methods: The CSF Aβ_1-42, 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 Aβ_1-42 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 Aβ_1-42 level does not exclude the C9ORF72 expansion associated with FTLD.

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“…Visual or auditory hallucinations, obsessive-compulsive disorder or psychosis (delusional psychosis, schizophrenia, bipolar disorder/hypomania) may precede or occur concomitantly to FTLD symptoms in 10% to 53% of mutation carriers [4,5,7,25]. Isolated episodic memory disorders at onset, mimicking Alzheimer's disease [26][27][28][29][30][31][32], and the logopenic variant of PPA [33] are rarely associated with c9orf72 expansion. Predominant amnestic disorders in patients with clinical diagnosis of Alzheimer's disease can be related to hippocampal sclerosis, detected in a significant proportion of c9orf72 pathological cases [30].…”

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confidence: 99%

Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion

Ber

2015

Revue Neurologique

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C9orf72 G4C2 repeat expansions in Alzheimer's disease and mild cognitive impairment

Cited by 70 publications

References 33 publications

Molecular genetics of early‐onset Alzheimer's disease revisited

Molecular genetics of early‐onset Alzheimer's disease revisited

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

Frontotemporal lobar dementia and amyotrophic lateral sclerosis associated with c9orf72 expansion

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