If surveying what is known of the pathology of age-related conditions, we find an array of cellular damage and metabolic waste accumulation that happens in everyone. The people with age-related medical conditions have a lot more of one or more types of this damage and waste, however. That is the root cause of their dysfunction and frailty. Aging isn't a linear process and damage causes further damage, so small differences early on can always snowball into large differences later. Accumulating damage and waste byproducts as the result of the normal operation of metabolism is common to all of us, and this makes it a good place to look for therapeutic targets. If spending billions and decades on medical research, better to emerge with a treatment that can benefit everyone.
Alzheimer's disease progresses hand in hand with the accumulation of amyloid-β (Aβ) in brain tissues. Much of the comparatively well funded field of Alzheimer's research is focused on clearing amyloid or interfering in the mechanisms thought to link it to cell death and neurodegeneration. There are plenty of other opinions in the field on the relevance of this approach, given that it is proving harder than expected to produce meaningful results in clinical trials, but for now that is where most of the funding goes. This will hopefully produce a technology platform for amyloid clearance, such as via immunotherapies, that can be generalized to clear the other score or so forms of amyloid that accumulate in tissues with advancing age. In some cases it isn't so clear as to exactly what harm they are causing, but they are not present in young tissues in significant amounts, so the prudent course of action is to remove them anyway. Clearance followed by observing the results will probably teach us more about their role in aging than the same amount of time and money spent on more conventional studies.
Amyloid accumulation takes place in everyone, not just those with enough resulting damage to officially qualify as an Alzheimer's patient. The dividing line isn't sharp at all: more amyloid correlates with more cognitive dysfunction, and at some point that tips over the margin. It isn't a road that anyone really wants to be on at all, of course, but nonetheless here we all are until new applications of medical science arrive to rescue us. That will require large amounts of funding and public support, both of which are presently far smaller in scale than they might be. Ours is a society that likes circuses and bonfires in preference to science and progress. When does the damage of aging start? It starts in youth, but takes decades to rise to the point at which it is noticeable. Here are two recent reports of research on this topic:
Scientists examined basal forebrain cholinergic neurons to try to understand why they are damaged early and are among the first to die in normal aging and in Alzheimer's. These vulnerable neurons are closely involved in memory and attention. Researchers examined these neurons from the brains of three groups of deceased individuals: 13 cognitively normal young individuals, ages 20 to 66; 16 non-demented old individuals, ages 70 to 99; and 21 individuals with Alzheimer's ages 60 to 95.
Scientists found amyloid molecules began accumulating inside these neurons in young adulthood and continued throughout the lifespan. Nerve cells in other areas of the brain did not show the same extent of amyloid accumulation. The amyloid molecules in these cells formed small toxic clumps, amyloid oligomers, which were present even in individuals in their 20's and other normal young individuals. The size of the clumps grew larger in older individuals and those with Alzheimer's. "This points to why these neurons die early. The small clumps of amyloid may be a key reason. The lifelong accumulation of amyloid in these neurons likely contributes to the vulnerability of these cells to pathology in aging and loss in Alzheimer's."
The medial temporal lobe is implicated as a key brain region involved in the pathogenesis of Alzheimer's disease (AD) and consequent memory loss. Tau tangle aggregation in this region may develop concurrently with cortical Aβ deposition in preclinical AD, but the pathological relationship between tau and Aβ remains unclear.
We used task-free fMRI with a focus on the medical temporal lobe, together with Aβ PET imaging, in cognitively normal elderly human participants. We found that cortical Aβ load was related to disrupted intrinsic functional connectivity of the perirhinal cortex, which is typically the first brain region affected by tauopathies in AD. There was no concurrent association of cortical Aβ load with cognitive performance or brain atrophy. These findings suggest that dysfunction in the medial temporal lobe may represent a very early sign of preclinical AD and may predict future memory loss.