Academic journal article General Psychiatry

More Is Needed before Alzheimer's Disease Can Be Conquered

Academic journal article General Psychiatry

More Is Needed before Alzheimer's Disease Can Be Conquered

Article excerpt

[Shanghai Arch Psychiatry. 2017; 29(4): 240-241. doi: http://dx.doi.org/10.11919/j.issn.1002-0829.217073]

German Neurologist Alois Alzheimer first reported the autopsy results of a fifty year old female patent named Auguste Deter in 1907. The patient presented with classic cognitive and behavioral disorder. The autopsy results showed two abnormal pathological changes: neurofibrillary tangles (NFTs) and senile plaques (SPs). In 1924 Divery found that SPs consisted of amyloid using Congo red staining. In 1984, Glenner and Wong purified a 4.2 kDa [beta]-amyloid (A[beta]) from a patent with Alzheimer's disease (AD) with cerebral amyloid angiopathy (CAA). The sequencing analysis showed A[beta] was a peptide containing 39-43 amino-acids, moreover A[beta]40 and A[beta]42 were main types. [1] Hardy and Selkoe proposed the amyloid cascade hypothesis in later years. Amyloid precursor protein (APP) severing disorder lead to over expression or less clearance of A[beta], and then A[beta] became aggregated. In particular, A[beta]42 accumulation caused synaptic degeneration, inflammation, oxidative stress, NFTs, neuron loss, and so on. [2] Not long afterwards, several massive, multidimensional, long-term clinical studies showed a relationship between A[beta] deposition in the brain and dementia using demic biomarker analysis. [3,4]

On the one hand, this may show why A[beta]-target strategies in AD drug development were always unsuccessful, but many pharmaceutical factories and labs still insisted on studying AD drugs because over the past 20 years of research a foundation for the pathological mechanism of AD has been established. Although its not necessary to completely start over, it is clear A[beta]-targeting drugs are not the final answer. In addition to what other researchers have reported in detail there are other ideas to consider. First, the neurophysiological and neurotoxic effects of A[beta] soluble monomer, oligomer and insoluble amyloid plaques are not clear. We have less knowledge about the clinical benefits of indiscriminate removal in passive immunotherapy. Second, A[beta] deposit in the brain begins ten years before clinical symptoms of dementia begin to appear This progress can also be observed in normal aged brains. Does A[beta] have a dramatic increase in AD brains compared to non-cognitive impairment (NCI)? Or are AD brain neurons more sensitive to A[beta], which leads to neural impairment and irreversible neuron apoptosis? We lack evidence for both of these questions. Third, although A[beta] and Tau are two individual pathological processes in AD, more and more results have shown relationships between them. …

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