(I should know better than to take the clickbait, but lapses do occur.)
The arguments have not changed much in the past 10 years, even if there has been some very modest success in clinical trials that remove amyloid from the human brain.
The question then, is why the amyloid hypothesis still remains popular among scientists and clinicians. The simplest reason is that it is currently the only way to mechanistically link the various genes whose mutation causes early onset Alzheimer's (APP and presenilin), i.e. that APP is the source of amyloid, and presenilin is needed to produce amyloid from APP. Both genetically inherited Alzheimer's and the more common form share too many pathological features to be considered entirely separate diseases.
Until there is an alternate explanation to mechanistically link presenilin, APP, and indeed apoE4, the amyloid hypothesis will always have its supporters.
[0] The case for rejecting the amyloid cascade hypothesis, Karl Herrup https://www.nature.com/articles/nn.4017
It should be named how not to write about how not to study a disease...
DaveZale•6mo ago
Long story short, the "magic bullet" approach of big pharma began with very simple antibiotics whose mission was to "take out the bad guys" like syphilus, TB, pneumonia, etc., with very simple drugs, some of them synthetic, some of them fungal products.
The amyloid hypothesis was an attempt to rationalize a correlation of higher amyloid in the brains of patients who died while afflicted with "Alzheimers" - so that small molecules or antibodies could target the amyloid.
Billions were spent. Patients died.
If you back up over a century to the work of Dr. Alzheimer, only a small fraction of today's AD patients actually have thr irregulataries he observed. But the US health care system provides compensation for medical services based upon "billing codes" - so the Alzheimer's disease diagnosis is a kind of umbrella diagnosis to get payment.
So the AD diagnosis is not the most scientific term in medicine, but involves patients with "dementia" or "senility" ... all terms for similar symptoms. What really underlies dementia? It can be brain damage, it can be vascular - hardening or occulsiom of arteries or the effects of stroke, it can be the long term effects of smoking or overeating for decades.
Our medical system is geared toward "magic bullet" thinking, which goes back over a century. But maybe there ara no magic bullets for AD. Maybe there are only lifestyle interventions which must be implemented decades before symptoms appear.
Of course, a few percent of true hereditary AD cases do appear, usually to patients that are younger. But for the vast majority, the true causes are varied and sometimes overlapping.