Old theories die hard — about Alzheimer's, among others

It seems that the cause of Alzheimer's disease is still widely accepted to be the build-up of plaques and tangles of protein in the brain. That theory has survived the failure of a succession of potential drugs that successfully removed plaques but did not produce cognitive improvement.

The New Scientist (October 21, 2023), which keeps track of the latest doings in science and medicine, reported what might have been another nail in the coffin of the plaque theory:

“They were considered flukes. Older people found upon their deaths to have brains full of the plaques and tangles associated with Alzheimer's disease, yet who had shown no signs of cognitive decline while alive. But then more cases appeared, and yet more. Something was protecting these people whose mental faculties remained bright, despite them facing the same destruction in their brain as others with memory loss, confusion and other signs of dementia.

 As more brains were analyzed, it was discovered that these cases aren't rare. Up to 30% of older people have enough plaques and tangles to be diagnosed with Alzheimer's, but never show any outward symptoms of the condition.”

The apparently favored explanation for this supposed conundrum involves “an enigmatic concept known as ‘cognitive reserve’  . . . A cushion of sorts, a barrier that slows the effect of damage.  Others liken it to the building of bypasses — alternate pathways for information to flow through when normal routes are destroyed.”

A simpler explanation would seem to be that those protein tangles and plaques are not the cause of Alzheimer's at all. Perhaps instead they are attempts to repair damage, attempts evidently quite successful in 30% of cases.

This would be analogous to cholesterol theory, the widespread belief that cardiovascular disease is caused by the accumulation of cholesterol plaques in the arteries brought about by an excess of cholesterol. Malcolm Kendrick^[1], however, has pointed out that the cholesterol in arterial plaques has accumulated there in order to cover scars or inflammatory damage to the artery wall: the cause of cardiovascular disease is the original damage or inflammation, while the cholesterol is available to help to repair the damage.

The explanation reported in New Scientist, of Alzheimer's symptoms apparently not determined by the protein plaques and tangles, seems far more complicated than necessary. But that is quite characteristic of science as well as medicine. Once a theory has become generally accepted by the experts, any apparent contradiction of the theory is met by ad hoc explanations that can later, in retrospect — or perhaps even in the light of ordinary common sense — be seen as not particularly likely.

An iconic case is Ptolemy’s astronomy, in which planetary movements were described by series of larger and smaller circles. All the wise men had been quite certain that heavenly motions must be circular, since that is the most perfect geometry. When actual observations could not be fitted into that scheme, further circles (epicycles) were added —  and added — leading us by hindsight, nowadays, to use the idiom of “wheels within wheels” to describe unnecessary complications, like those also featured in Rube-Goldberg machines and Heath-Robinson contraptions.

Ad hoc attempts to maintain a failing theory illustrate another generalization, that no once-accepted theory is abandoned before a fully satisfactory alternative is conceived. In the meantime, adherents to the old theory argue with critics, until eventually a new comprehensive theory wins the day in what Thomas Kuhn[2] called a “scientific revolution”; albeit Max Planck pointed out that the Old Guard would often fail to embrace the new theory, so that the latter would not or could not become fully established until the members of the Old Guard had passed away.

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[1]     Kendrick, Malcolm. The Clot Thickens: The enduring mystery of heart disease. Columbus Publishing, 2021; ISBN-13:‎ 978-1907797767

[2]     Kuhn, Thomas. The Structure of Scientific Revolutions, University of Chicago Press, 1962 (2^nd edition, with postscript, 1970).

[1]     Kendrick, Malcolm. The Clot Thickens: The enduring mystery of heart disease. Columbus Publishing, 2021; ISBN-13:‎ 978-1907797767

[1]     Kuhn, Thomas. The Structure of Scientific Revolutions, University of Chicago Press, 1962 (2^nd edition, with postscript, 1970).