A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and alzheimer disease

TLDR

The causes of ALS, Parkinson’s disease, and Alzheimer’s disease are unknown, and treatment for two of these conditions is almost totally lacking. The study proposes that ALS, Parkinson’s disease, and Alzheimer’s disease result from a deficiency of disorder‑specific neurotrophic hormones. The hypothesis posits that a disorder‑specific neurotrophic hormone is produced or stored in target neurons, released by postsynaptic cells, taken up by presynaptic terminals to act retrogradely, and can be assayed in CNS tissue culture. Deficiencies of motor neuron, dopamine, and cholinergic neurotrophic hormones in ALS, Parkinson’s disease, and Alzheimer’s disease respectively lead to impaired anterior horn, substantia nigra, and medial septal/nucleus basalis neurons.

Abstract

Abstract The causes of amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are unknown. Furthermore, treatment for two of these conditions is almost totally lacking. The thesis is presented that each of these disorders is due to lack of a disorder‐specific neurotrophic hormone. The hormone would be elaborated or stored in the target of the affected neurons. It would be released by the postsynaptic cell and then exert its effect in a retrograde fashion after being taken up by the presynaptic terminal. In the lower motor neuron syndromes of amyotrophic lateral sclerosis, failure of muscle cells to release the appropriate motor neuron syndromes of amyotrophic lateral sclerosis, failure of muscle cells to release the appropriate motor neurotrophic hormone would result in impaired function of anterior horn cells. In Parkinson disease, the neurotrophic failure would be characterized by inability of striatal cells to provide the required dopamine neurotrophic hormone with resulting impairment of substantia nigra cells. In Alzheimer disease, the abnormalities would lie in failure of the hippocampus and cortical cells to supply the relevant cholinergic neurotrophic hormone with resulting impairment of medial septal and nucleus basalis neurons. Central nervous system tissue culture provides a convenient system in which to assay these neurotrophic hormones and should permit a test of the hypothesis.