[Alzheimer's dementia and zinc]

In Alzheimer's dementia (AD) the Primum Movens is Amyloid (AM) production on precapillaries: Dyshoric Angiopathy, and capillaries: Senile Plaques (SP) producing Blood-Brain-Barrier (BBB) disturbances, entry in the brain of toxic metals which displace the zinc. Cerebral AM alone may be asymptomatic. Clinical symptoms (Amnesia, Instrumental Disorders) appear when AM induces Neighbouring neuritic alterations: Paired Hellical Filaments (PHF) and Distant neuronal body lesions: Neurofibrillary Tangles (NFT). The AM is coded by a locus on the chromosome 21 and a duplication of this locus should be the etiology of cerebral AM in AD. In AD cerebral zinc decreases particularly in the hippocampus. The zinc-enzyme Superoxyde-Dismutase (SOD) is coded by a locus also on the chromosome 21 near AM and the plasma level of SOD is high in AD. Zinc deposits observed in capillary AM-SP, result probably from the excess of plasmatic SOD. Other metals: Iron, aluminium are also observed in the AM-SP and their excess in the brain may be related to the decrease of zinc by metal to metal displacement. The decrease of functional zinc in the brain may interfere in the pathogenesis of PHF-NFT by metalotoxicity, neighbouring and distant to AM. Without AM, NFT are produced also by metalotoxicity and therefore brain zinc displacement. a) by lead: Encephalopathia saturnica b) by many metals: Guam Encephalopathy c) by aluminium d) by BBB disturbances leading probably to an abnormal entry of metals in the brain (Dementia Pugilistica, viral encephalitides). NFT may be produced by the deficiency of the following zinc enzymes: 1. Those of DNA metabolism, indicating abnormal DNA and therefore abnormal protein synthesis: PHF-NFT. 2. Those of neuronal detoxication: SOD, Carbonic Anhydrase, Lactate Dehydrogenase leading to neuronal toxicity particularly in the hippocampus normally rich in SOD. 3. Of Glutamate (GLU) Dehydrogenase (GDH) resulting in an excitotoxic increase of GLU. 4. Those of the metabolism of neurotransmitters (NT): neuropeptides, Histamine, GABA, Acetylcholine. Therapeutic proposition: a zinc complex crossing the BBB should be useful a) to prevent that the AM produces PHF-NFT by Neighbouring and Distant metalotoxicity and DNA changes; b) to regularise zinc-enzymes of neuronal detoxification and of neurotransmitters metabolisms. Preliminary trials by zinc Aspartate give yet promising results.