Alzheimer's disease is perhaps the most studied form of age-related neurodegeneration. About 40% of the yearly budget of the US National Institute on Aging goes towards research into Alzheimer's disease, for example, and that is just the easily discovered funding. Where there is work on treating Alzheimer's rather than further investigating it, that research tends to focus on clearing clumps and fibrils of misfolded proteins known as amyloid. Alzheimer's is accompanied by a characteristic build up of amyloid beta, which many researchers think is the proximate cause of the harm the condition does to the brain. You might look at ongoing attempts to direct a patient's immune system to clear amyloid from the brain, for example.
Neural biochemistry is enormously complex, however, and there is plenty of room for uncertainty and argument over the root causes of Alzheimer's, how it progresses, and exactly which mechanisms are damaging and destroying brain cells. Why do some people suffer Alzheimer's while others do not, for example, even though we all appear to progress down the same path general of amyloid buildup and cellular damage? Here is an open access review paper that surveys the current range of plausible theories:
Ever since the first description of pre-senile dementia by Alois Alzheimer in 1907, the presence of cognitive impairment together with the formation of senile plaques (SP) and neurofibrillary tangles (NFT) have been regarded as the [defining] features of Alzheimer's disease (AD). Many theories as to the cause of AD have [been] proposed. It is not the intention to discuss every theory but to concentrate on those most likely to be involved. Hence, the theories are discussed in eight categories: (1) acceleration of aging, (2) degeneration of anatomical pathways, including the cholinergic and cortico-cortical pathways, (3 environmental factors such as exposure to aluminium, head injury, and malnutrition, (4) genetic factors including mutations of amyloid precursor protein (APP) and presenilin (PSEN) genes, and allelic variation in apolipoprotein E (Apo E), (5) a metabolic disorder resulting from mitochondrial dysfunction, (6) vascular factors such as a compromised blood brain barrier, (7) immune system dysfunction, and (8) infectious agents. This review discusses the evidence for and against each of these hypotheses and develops a general theory as to the cause of AD.
That AD may be an accelerated form of natural aging is based on the observation that the many pathological changes in AD are similar to those present in normal aging apart from their severity. Hence, in cognitively normal brain, there is an age-related reduction in brain volume and weight, enlargement of ventricles, and loss of synapses and dendrites in selected areas. Accompanying these changes are the characteristic pathological features of AD, including SP and NFT. Studies of Aβ deposition have also demonstrated a clear overlap between AD and normal aging. It was concluded that it was not possible to distinguish early-stage AD from normal aging at post-mortem. Similarly, SP have been observed in 60% of normal elderly cases, albeit at lower density than in AD. Moreover, [researchers have] concluded that there could be a 'continuum' of pathological change from elderly non-demented brains, early stage AD, to advanced AD.
Whether NFT occur as a result of normal aging is more controversial, [however]. Two further aging processes may be involved in AD. First, an age-related breakdown of myelin, although other studies suggest that myelin loss occurs late in AD and is secondary to neuronal degeneration. Second, the loss of cells in the locus caeruleus (LC), which provides noradrenaline to the cortex [and] stimulates microglia to suppress production of Aβ.
These studies suggest that the differences between AD and the normal elderly are largely quantitative rather than qualitative and there may be a 'continuum' of pathological change connecting these cases. Nevertheless, the distribution of the pathology may differ in AD and control brain, being more localised to areas of the temporal lobe in aging and with a more extensive spread into the hippocampus and cortical association areas in AD. An important question, therefore, is whether AD is an exacerbation of normal aging resulting from enhanced spread of the pathology along anatomical pathways.