TY - UNPB
T1 - pTDP-43 aggregates accumulate in the gut and other non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis
AU - Pattle, Samuel B.
AU - O'shaughnessy, Judi
AU - Rifai, Olivia M
AU - Pate, Judith
AU - Arends, Mark J.
AU - Waldron, Fergal
AU - Gregory, Jenna
PY - 2022/3/19
Y1 - 2022/3/19
N2 - Neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non-central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of TDP-43 pathology in archived non-CNS tissues, taken as part of routine clinical practice during life from people with ALS. We identified pTDP-43 aggregates in multiple cell types of the GI tract (i.e., colon and gallbladder), and within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non-CNS pTDP-43 pathology, aggregates were present prior to ALS diagnosis (median=24months) and, in some instances, preceded neurological symptom onset by more than 10years. These data imply that patients with non-CNS symptoms may have occult protein aggregation tha could be detected many years prior to neurological involvement.
AB - Neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non-central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of TDP-43 pathology in archived non-CNS tissues, taken as part of routine clinical practice during life from people with ALS. We identified pTDP-43 aggregates in multiple cell types of the GI tract (i.e., colon and gallbladder), and within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non-CNS pTDP-43 pathology, aggregates were present prior to ALS diagnosis (median=24months) and, in some instances, preceded neurological symptom onset by more than 10years. These data imply that patients with non-CNS symptoms may have occult protein aggregation tha could be detected many years prior to neurological involvement.
U2 - 10.1101/2022.03.17.484805
DO - 10.1101/2022.03.17.484805
M3 - Preprint
BT - pTDP-43 aggregates accumulate in the gut and other non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis
PB - bioRxiv
ER -