Louisville Medicine Volume 69, Issue 8 - Page 14

AUTHOR Vasudeva Iyer , MD


AUTHOR Vasudeva Iyer , MD

2020 and 2021 have been the dark and depressing years of the pandemic , and the medical world has been consumed by attention to various aspects of the SARS- CoV-2 infection . But a silver lining in the gloom is that there has been significant progress in our understanding one of the most dreaded and prevalent diseases of the senior citizens , Alzheimer ’ s disease ( AD ). I was thrilled to read about a commercially available blood test for Alzheimer ’ s and the approval , albeit controversial , by the FDA of a new drug for disease modifying treatment . However , my enthusiasm was tempered by a tinge of skepticism , as over the years there have been so many promises for diagnosis and treatment of dementia , which have then gone by the wayside . First , I want to recall the fascinating history of Alzheimer ’ s disease and glide down the path to the new and exciting developments .

Alois Alzheimer was born in Marktbreit , Germany in 1864 . He started his medical career at the Community Hospital for Mental and Epileptic patients in Frankfurt am Main . In 1901 he began treating Auguste D , whose symptoms included paranoia , memory disturbance , aggressiveness and sleep disorder ; he doggedly followed her progress until her death in 1906 , even after he had moved to Munich . By then to his credit , he had organized a modern histopathology lab . D ’ s brain was studied in detail by Alzheimer . He described the now well-known plaques and tangles and presented details at the German psychiatrists ’ conference , but to his dismay these did not arouse much enthusiasm . However , his colleague Emil Kraepelin used the term Alzheimer ’ s disease ( a commendable gesture !) in his textbook published in 1910 to describe the condition . Alzheimer in 1911 studied histopathology of another patient , Johann F , whose brain showed plaques , but no
neurofibrillary tangles . There has been debate as to whether Johann F had the same disease as Auguste D , and if so , why no tangles . The controversy was settled after heroic efforts to retrieve the original slides of Johann F , which remarkably survived the world wars . Scientists succeeded in examining the slides in 1995 and the conclusion was that Johann ’ s brain represented the “ plaque only ” form of Alzheimer ’ s disease .
I used to imagine that the world of neurology is cursed with three Darth Vaders ( influence of watching Star Wars with my son ): ALS , Parkinson ’ s disease , and Alzheimer ’ s disease . When reports of all three diseases occurring in the Chamorro people in Guam surfaced , there was considerable glee that a common cause would soon be found leading to potential treatment . The Guamanian neurodegenerative disease ( local name is Lytico-bodig disease ; subject of part 2 of Oliver Sacks ’ book , The Island of the Colorblind ) was expected to be the “ skeleton key , a neurologic Rosetta stone .” 1 There have been numerous scientists spending countless research-years on this disease , but no one emerged as the champion ( like Jean-Francois Champollion , who deciphered the Rosetta stone ), and all ended up with speculations and theories .
Like most elderly , physicians also get anxious when they start having difficulty with recalling names , telephone numbers or forget to switch off lights or other familiar chores . They wonder whether they themselves are having the first signs of Alzheimer ’ s disease . I have noticed that older neurology colleagues relish in testing each other for cognitive decline during annual meetings ( dinner dialogue ). The 2020 challenge was to expand the acronym CRISPR ( Clustered Regularly Interspersed Short Palindromic Repeats ; some of you may recall that J . Doudna and E . Charpentier won 2020 Nobel prize in Chemistry for discovering this technique of gene editing ).
It is estimated that there are 5.8 million individuals in the U . S . with Alzheimer ’ s disease and that the number will increase to 14