One hundred years of Alzheimers disese

Published in   JFWTC in house Journal Vol.2 Issue 3 2006

Nov. 3^rd issue of Science carries several interesting articles on  Alzheimer’s disease.  It was exactly 100 years ago on 3^rd Nov. 1906 that  Dr Alois Alkzheimer  presented a detailed  paper on this   bewildering  disease. The occasion was the  37^th meeting of the German psychiatrists  in Tubingen, Germany. The papers collectively   read almost like “One hundred years of solitude” by Garcia, peep into the developmental biology of this debilitating disease.  

As the head of the anatomical laboratory of a psychiatric clinic, Alzheimer and his team had  observed  intriguing   protein patches  in   epilepsy patients during brain histopathology studies.   In April  1906 one of his female patients  afflicted with  progressively deteriorating  mental faculties   died and the subsequent neuro pathological studies revealed the presence of patches and tangles  in her brain.  This was a sort of clinching evidence for Alzheimer , whose notebook contained entries  after entries of  mentally ill and epileptic patients  and their brain histopathology reports.  He now had enough proof to make the connection: accumulation of debris in the brain to deteriorating mental faculties.

But that was 1906 and only the beginning of understanding Alzheimer’s disease.   While it might have been easy to identify the chemical nature of the protein, b amyloid,  ( now we know it a short polypeptide 40 or 42 residues long , trimmed to size from a larger  precursor) , it has taken several  decades to understand  “how” and the “why” is still shrouded in mystery.  Besides the b amyloid protein  which deposits as the patches, our current knowledge implicates another candidate:  the highly phosphorylated forms of t (Tau) protein which forms the fibrillar tangles.  But there are several unanswered questions. Brain has at least 6  forms of t protein and all six  have other essential functional responsibilities as  stabilizing agents for   “ microtubular assembly” which are structural components of a cell.. So when does Dr Jekyll become Mr Hyde? And more importantly what is the   link  between b amyloid and t proteins.  Do they work independently or in collusion?

Age appears to be the major predisposing  factor while inherited forms  of the disease  are rather rare,  less than 1% . Statistics paints a horrifying picture of the disease spreading like wildfire. Already we are being challenged with a physically  aging population, add to that dementia.   Scientists are pushing hard for a weapon to face and subdue disease. Blocking the overproduction of the causative proteins using drugs could be one way  which is the current method.   However, it has also been noticed that this blocking upsets several other delicate biological balances within the body.  That calls for more elaborate efforts in drug design. Time is not on our side here given that each drug has to go through several phases of testing, often spanning several years before it is certified

Of course the best  remedy is to spot the patches and fibrils at the molecular level and contain it then and there. We are not there yet, but soon will be.   Or perhaps one could use cleverly the “ silencer genes” ( Nobel Prize 2006 for Physiology & Medicine) to turn off  (and on as often as necessary) the  b amyloid  and t protein genes.