About this Research Topic
While aging alone is generally agreed to be sufficient for at least the preclinical state of PD, the situation in AD seems to be different. Aging as the major and well documented risk factor of AD has been neglected for decades. Biochemical mechanisms of brain aging and the cognitive deficits of “normal brain aging” were seen as two not related and independent processes not related to AD. AD has always been characterized for decades by the presence of histopathological alterations (extracellular amyloid- containing plaques and intracellular tangles of hyperphosphorylated tau-protein), by neurodegeneration (synaptic deficits and finally neuronal loss), as well as by severe cognitive deficits clinically often accompanied by neuropsychiatric symptoms like delusions, as already described in the first famous patient Auguste D at the Psychiatric Hospital of Frankfurt.
If or if not one or both of the two histopathological hallmarks play a causative role remains unclear until now. The discovery of homocygotic risk genes in most of the very rare (probably less than 1%) cases of early onset AD which share increased production of β-amyloid (Aβ) as one (but probably not the only one) common property led to the hypothesis of Aβ as the major causative factor for the development of AD. It was neglected that plaques density in the brain of AD patients did not correlate with presence and severity of clinical symptoms, while synaptic deficits did so even in first observations already published many years ago.
Based on the Amyloid hypothesis, many drug treatments to remove Aβ plaques were developed. Even if all seemed to remove Aβ to some extent, all strategies failed to improve the symptoms of dementia. Thus, other concepts to explain the development of clinical symptoms of AD over time are needed. These should include the brain aging process not only as a statistical but also as a causative contributing factor. These concepts should not only relay on cell or animal models but should much more take into account the disease and the patients. A closer look at the situation in PD will certainly be helpful.
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