We investigated 185 families with ALS for evidence of anticipation and mitochondrial inheritance. Although initial analysis demonstrated significant anticipation of age at death between generations in patients with familial ALS, further analysis demonstrated features of regression to the mean, suggesting that the perceived differences are the result of bias. In addition, there was no evidence of an effect of preferential maternal inheritance, which would have supported transmission of mitochondrial DNA mutations.
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http://dx.doi.org/10.1212/01.WNL.0000160395.43761.AC | DOI Listing |
Nat Commun
January 2025
Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Delaware State University, Dover, DE, USA.
Background: Aggregation of transactive response DNA binding protein 43 (TDP-43) is the major pathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recently, in up to 50% of Alzheimer's disease (AD) cases TDP-43 pathology was discovered and this pathology has been referred to as limbic-predominant age-related TDP43 encephalopathy (LATE). Several studies reported that TDP-43 binds to heat shock protein family B (small) member 1 (HSPB1 or HSP27) but no functional evaluation of this interaction has been explored.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Delaware State University, Dover, DE, USA.
Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by upper and lower motor neuron death that leads to paralysis with the average survival being 3-5 years after diagnosis. The major pathological protein in ALS is TDP-43. TDP-43 becomes hyperphosphorylated and forms inclusions mainly in the cytoplasm.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Koc University, Department Biology and Genetics, Istanbul, Turkey.
Background: Valosin Containing Protein (VCP) mutations are responsible some genetic etiologies of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Method: A 67-year-old, male patient, applied to the clinic due to behavioral changes and difficulty swallowing. According the patient history it was reported that his first complaint started 6 years ago (at the age of 61).
Alzheimers Dement
December 2024
Memory and Aging Center, UCSF Weill Institute for Neurosciences, San Francisco, CA, USA.
Background: The ALLFTD (ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration) study is an NIH-funded effort to prepare for clinical trials in sporadic (s-FTLD) and familial (f-FTLD) FTLD syndromes by characterizing cohorts, developing new clinical trial outcome measures, and evaluating disease progression. To understand disease trajectories in the context of potential preventative or disease-modifying therapeutic agents, comprehensive evaluation across multiple time-points is crucial.
Method: ALLFTD evaluates participants with FTLD spectrum disorders (bvFTD, svPPA, nfvPPA, FTD-ALS, CBS, PSP), with strong family histories of FTLD, or known FTLD-associated genetic variants within the family.
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