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Heterogenity of Alzheimer's Disease


H.H. Fudenberg MD Molecular Neurobiology 9:55-71 (1994)

Forty patients with severe Alzheimer's Disease and five with mild Alzheimer's Disease were studied. Biologic markers were found for three different subsets and none in a small fourth subset, indicating heterogeneity in etiology and/or pathogenesis. The subsets thus defined by biologic membrane responded differently to different therapies. Patients in one subset, those with diminished membrane flexibility, responded well to pyrrolidinone compounds with regain of rectal and bladder sphincter function, ambulatory capacity, and speech when treated with pyrrolidinone but relapsed on placebo in both single blind and double blind trials. Patients with aberrant immune function as indicated by lymphocyte DNA synthesis in PHA, response to 1 acid glycoprotein, and autologous mixed leucocyte reaction, and antibodies to neuron axon filament protein improved on large doses of dialyzable lymphocyte extract enriched in transfer factor (DLyE) but improvement was transient, averaging three to four weeks, except when huge amounts were administered. Some evidence indicates prions as an etiologic agent in this subset.

A third subset was characterized by IgG3 auto-antibodies to cerebral cells; preliminary data indicated that such patients would respond to immunosuppressant agents such as those used in treatment of lupus, Erythematosus, and other auto-immune conditions.