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Med Hypotheses. 2007;69(5):1135-9. Epub 2007 May 11.

Prolonged stress will induce Alzheimer's disease in elderly people by increased release of homocysteic acid.

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Saga Woman Junior College, Saga 840-8550, Japan.


Recently, many papers have reported the physiological functions of amyloid beta and amyloid precursor protein (APP). In particular, one of its functions is of importance for synaptic plasticity. Extracellular amyloid beta may suppress synaptic plasticity or inhibit long-term potentiation (LTP) from outside the cell. LTP is now considered the molecular basis of memory. Amyloid beta may induce the inhibition or loss of memory. We propose that suppression of LTP by amyloid beta induces a kind of physiological forgetfulness. On the other hand, homocysteic acid (HA) which is released from astrocytes under stress conditions accumulates the amyloid beta into neuronal cell, which consequently induces the inhibition of amyloid beta physiological function and induces strong LTP. We propose that HA induces strong unforgetful memory under stress condition such as PTSD and emotional depression. The situation is different in the elderly people. Prolonged stress in the elderly people may induce neurodegenerative diseases such as Alzheimer's disease. We observed that in the presence of excess methionine, HA induced alpha-synuclein protein in cultured cells, suggesting a hypermethylation model in vivo. Usually hypermethylation is observed in the ageing process. We have shown that HA promotes the accumulation of amyloid beta in cells, and that the production of alpha-synuclein, which induces the aggregation of amyloid beta, impairing the cell function. LTP is inhibited by deficient cellular function, which means that memories cannot be formed. In fact, there is confusion of memories in the early stages of Alzheimer's disease. Finally, the aggregated alpha-synuclein induces tau pathology, which induces cell death, leading to Alzheimer's pathology. In conclusion, we propose that HA induces Alzheimer's pathology in the elderly people because of prolonged stress.

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