Association of Alzheimer's disease and amyotrophic lateral sclerosis: A series of cases and review of the literature

Abstract

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is a sporadic or familial fatal neurodegenerative condition that affects motor neurons in primary motor cortex, brainstem and spinal cord. While predominantly a motor disorder, ALS is frequently associated with cognitive impairment, mostly of frontal type. Hippocampic syndrome is not recognized as part of the cognitive phenotype of ALS.MethodAfter a national translational survey, we report a French multicentric case series of three patients that presented with an association of definite Alzheimer disease (AD) and ALS. A systematic review of the literature was carried out in January 2020 to explore already reported similar cases.ResultPatient n°1 had a history of behavioral variant of AD followed seven years later by onset of bulbar ALS. Cerebro‐Spinal Fluid (CSF) AD biomarkers displayed AD biological profile associated with ApoE4E4 genotype. Genetic testing for C9ORF72 expansion was negative. Patient n° 2 was diagnosed with ALS, associated with dysexecutive syndrome and CSF AD biological profile (Wallon et al, 2012). Patient n°3 had clinical AD and ALS. Post‐mortem analysis was available, confirming motoneuron disease and Alzheimer type pathology. Review of the literature retrieved only few other cases of co‐occurence of AD and ALS (Nijboer et al, 2019; Farid et al, 2015; Müller et al, 1993). More frequently, association of amyloid pathology to ALS lesions at post‐mortem examination has been described in ALS patients with or without cognitive impairment. Nevertheless, the relationship between these findings and clinical manifestations is still unclear. The mechanisms that account for the underlying neurodegenerative processes that occured in our patients remain to be comprehended.ConclusionWe report a series of cases associating AD and ALS and discuss the hypothesis of it being an under recognized phenotype.