An Assessment of Possible Neuropathology and Clinical Relationships in 46 Sporadic Amyotrophic Lateral Sclerosis Patient Autopsies

Abstract

Background: Recent studies have suggested overlapping pathological features among motor neuron, cognitive and neurodegenerative diseases.

Aims/methods: Secondary analysis of 46 amyotrophic lateral sclerosis (ALS) patient autopsies was performed to independently assess pathological feature prevalence (e.g. percent of patients with any positive finding), degree of severity (e.g. mild, moderate, severe), and 2,200+ potential clinical/neuropathological correlations. The possible impact of gender, onset age, onset type (limb vs. bulbar), riluzole treatment, and severe TDP-43 pathology was assessed within patient subgroups.

Results: Assessed features (prevalence, severity) include: lateral corticospinal tract degeneration (89%, moderate); Purkinje cell loss (85%, mild); localized neuronal loss (83%, mild to moderate); TDP-43 inclusions (80%, moderate); Betz cell loss (76%, mild); neurofibrillary tangles (78%, severe); anterior corticospinal tract degeneration (72%, moderate); spinal ventral root atrophy (65%, moderate); atherosclerosis (35%, mild); β-amyloid (35%, mild); tauopathy/tau inclusions (17%, mild); ventricular dilation (13%, mild); Lewy body formation (11%, mild); microinfarcts (7%, mild); and α-synuclein (4%, mild). Twenty-two percent of patients met criteria for Alzheimer's disease (AD) and 26% for frontotemporal lobar degeneration. Substantial differences were identified in the AD group and in the different onset age groups.

Conclusion: Our findings support the hypothesis that ALS and its variants could comprise a larger neuropathological continuum.