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he present invention is based on the discovery that amyotrophic lateral sclerosis (ALS), Parkinson disease and Alzheimer disease are due to lack of a disorder-specific neurotrophic hormone. Diagnosis is accomplished by assaying hormones specific for a particular neuronal network or system: the motor neurotrophic hormones from muscle in the motor neural system are used to diagnose and treat ALS, dopamine neurotrophic hormones from striatum in the nigrostriatal neural system are used to diagnose and treat parkinsonism, and cholinergic neurotrophic hormones released from the cortex and hippocampus which are specific for cholinergic neurons of the nucleus basalis and septal nucleus are used to diagnose and treat Alzheimer's disease. With tissue culture, the presence or absence of specific neurotrophic hormones can be assessed in ALS, parkinsonism, and Alzheimer disease. If there is a deficiency, extracted and purified neurotrophic hormones specific to the particular neuronal network or system can be injected in ALS and Alzheimer disease and in parkinsonism. Alzheimer disease is a disorder of the later decades of life characterized by dementia. In clinical terms, it consists of a diffuse deterioration of mental function, primarily in thought and memory and secondarily in feeling and conduct. Alzheimer disease has been used to designate dementia appearing before the age of 65 years. When the syndrome presents after that age, the term senile dementia of the Alzheimer type is used. In fact, it appears reasonable to consider both types as representing a single syndrome. The true incidence of the disorder is unknown, although recent data suggest that the incidence of all dementia in the U.S. population may be over 100 cases per 100,000, with its prevalence being over 550 per 100,000 [12]. Alzheimer disease probably affects at least 30 to 50% of patients with dementia, and in the United States there may be over one million individuals with severe dementia and several million more with mild to moderate dementia. It has been estimated that 1 out of every 6 persons over the age of 65 in the United States suffers from moderate dementia, and a majority of patients in nursing home populations are affected with the disorder. The average age of onset is between 70 and 79 years, but without better information on the population at risk, a more accurate statement is not presently possible [12]. As in ALS and parkinsonism, the incidence of the syndrome clearly increases with advancing age. A family history of Alzheimer disease is present in 5 to 10% of the patients. At the present time, the clinical diagnosis of Alzheimer disease is one of exclusion. Secondary causes of loss of memory and impaired cognitive function may result from multiple infarcts, leading to so-called multiinfarct dementia, or from intracranial mass lesions such as subdural hematomas, brain tumors, or granulomas. Central nervous system infections of viral and bacterial origin, or even slow viral disorders such as Jakob-Creutzfeldt disease, are part of the differential diagnosis. Furthermore, metabolic disorders involving vitamin B 12 metabolism, thiamine or folate deficiency, thyroid dysfunction, hepatic and renal failure, as well as drug toxicity may present as dementia. Nevertheless, when all these secondary causes, many of which are reversible, are eliminated, cerebral atrophy of unknown cause or Alzheimer disease still covers the largest number of patients. Elevations of aluminum content in brain have been implicated in the pathogenesis of the disorder but appear to be secondary rather than primary [13, 14]. The pathological picture of Alzheimer disease has been well characterized over the years. It consists of senile plaques, which result from degeneration of nerve endings, and neurofibrillary tangles, which represent an alteration in the cytoskeletal apparatus [15]. In addition, intracellular cytoplasmic eosinophilic inclusions, termed Hirano bodies, are present, primarily in the hippocampus. Granulovacuolar degeneration is also noted. Senile plaques and neurofibrillary tangles in the brain are part of the "normal" aging process. However, at any age, patients with clinical Alzheimer disease appear to have a much higher concentration of these abnormalities than do normal individuals [16]. The most recent prominent discovery in Alzheimer disease is a deficiency of the enzyme that synthesizes the neurotransmitter acetylcholine, namely, choline acetyltransferase (CAT) [17]. This deficiency is most marked in the cortex and hippocampus. Of note is the fact that acetylcholine receptors in the brain are either unaffected or relatively less affected. Thus, the defect in CAT reflects an alteration in the presynaptic cholinergic neuron. The diminution in CAT correlates with the presence of senile plaques: the greater the number of plaques, the lower the activity of CAT. Enzymes synthesizing several other neurotransmitters including dopamine, norepinephrine, serotonin, and y-aminobutyric acid, as well as levels of vasoactive intestinal peptide, are all relatively unaffected compared to the loss of CAT activity. Somatostatin-like activity has recently been reported to be decreased in cerebral cortex [18]. The CAT activity found in hippocampus appears to derive
largely from nerve terminals for which the cell of origin is in the septal
nucleus. In addition, almost 70% of CAT activity in the cortex appears
to reside in terminals with cell bodies located in the nucleus basalis
of Meynert [19]. In rats, these cholinergic neurons lie intermingled with
and beneath the medial globus pallidus, whereas in primates, comparable
cells are found exclusively outside the pallidum. In humans, the nucleus
basalis of Meynert is situated in the fibrous zone beneath the globus pallidus
and is a major component of the substantia innominata [20]. Thus, the cholinergic
input to hippocampus and cortex may derive from a group of cells extending
from the septal nuclei to constituents of the substantia innominata and
may well be impaired in Alzheimer disease [20].
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