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Neurosurgery can save the World from Alzheimer’s disease
Presenting Author: Javed Siddiqi, MD, DPhil (Oxon), FACS, FRCSC,
FAANS
Original Research Pre-Print Authors on medRxiv (BMJ), 2021: Ricardo Zara-
goza, Daniel Miulli, Samir Kashyap, Tyler A. Carson, Andre Obenaus, Javed
Siddiqi, Douglas W. Ethell
Alzheimer’s disease is the holy grail of healthcare, with 44 million patients, and
no cure. Another 250 million cases are expected by 2050, when Alzheimer’s
disease will threaten the solvency of healthcare systems worldwide, costing
more than a trillion dollars annually in the US alone. With billions lost and dec-
ades wasted on the fruitless pursuit of therapies centered on the “Amyloid
hypothesis,” Alzheimer’s disease research desperately needs a reset. Here we
present evidence that disrupted CSF flow plays an apical role in Alzheimer’s
disease etiology. The disease progresses due to a self-perpetuating pathology
that forms first in the medial temporal lobe. This archaic brain region still relies
on the olfactory system to clear metabolite-laden CSF.
In evaluating the final outlet for that flow-the cribriform plate-in >600 sub-
jects from 20-94 years old, we found age-dependent occlusion restricting CSF
egress. Further, this loss of cribriform plate porosity was most dramatic in Alz-
heimer’s disease patients. To test this hypothesis, we occluded the cribrose
apertures in ferrets. We found that it induced progressive deficits in spatiotem-
poral memory and atrophy of the medial temporal lobe (homolog) over six
months. Our team has developed a non-invasive, AI-based, proprietary pro-
cess that uses cribriform plate morphology and cognitive testing to predict,
years before cognitive impair begins, who will get Alzheimer’s disease and
when. Once we predict who is at risk of cognitive impairment, we have a way
to fix it—we present a neurosurgical procedure to restore CSF clearance of the
olfactory system and stop Alzheimer’s disease pathology at its source.

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