Neurodegenerative disorders are characterized by disruptions to neuronal function and circuitry, leading to a variety of clinical syndromes depending on the affected neuroanatomic regions (Geula, 1998). Many proteinopathies implicated in neurodegenerative diseases are characterized by the pathologic accumulation of proteins into inclusions that are initially deposited in specific areas of the brain and spread widely with disease progression, leading to significant neuronal loss and gliosis (Brettschneider et al., 2013, 2014; Josephs et al., 2016; Jamshidi et al., 2020). There is substantial evidence that amyloid-β, phosphorylated tau, and α-synuclein spread through cell-to-cell propagation of pathological seeds in a prion-like manner, most likely involving trans-synaptic spread of pathology (Brettschneider et al., 2013). In recent years, research has begun to address the mechanism of propagation underlying the transactive response DNA-binding protein 43-kDa (TDP-43) abnormal species of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) (Brettschneider et al., 2013). In a recent study, our laboratory produced evidence suggesting that TDP-43 inclusions spread throughout the hippocampus in a manner that supports transsynaptic propagation along axonal pathways (Jamshidi et al., 2020). Here, we briefly review prior research on the propagation of TDP-43 pathology and suggest putative mechanisms.

Mesulam Center for Cognitive Neurology and Alzheimer's Disease,Feinberg School of Medicine,Northwestern University,Chicago,IL,USA;Department of Psychiatry and Behavioral Sciences,Feinberg School of Medicine,Northwestern University,Chicago,IL,USA;Department of Pathology,Feinberg School of Medicine,Northwestern University,Chicago,IL,USA;Department of Physiology,Feinberg School of Medicine,Northwestern University,Chicago,IL,USA

[1]Rachel Keszycki;Pouya Jamshidi;Allegra Kawles;Grace Minogue;Margaret E.Flanagan;Colleen R.Zaccard;M.-Marsel Mesulam;Tamar Gefen;Changiz Geula-.Propagation of TDP-43 proteinopathy in neurodegenerative disorders)[J].中国神经再生研究（英文版）,2022(07):1498-1500

proteinopathy,neuroanatomic,Geula,proteinopathies,gliosis,Brettschneider,Josephs,Jamshidi,transsynaptic

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