Re: Alzheimer's and Parkinson's--a cure, a corelation?

	Well Brian, this is a very good question, but unfortunately, it 
would be impossible to fully answer it in the space allotted in this forum, 
but I will briefly discuss some topics.  I suggest picking up a recent copy 
of a neurological textbook if you are really interested in all the facts.  
	AD and PD have historically been recognized as two separate 
neurological disorders.  Idiopathic AD is a dementia associated with 
characteristic histopathological changes in the brain: senile plaques and 
neurofibrillary tangles.  Senile plaques (SP) are extracellular deposits of 
amyloid protein and neurofibrillary tangles (NFT) are intracellular 
inclusions of paired helical filaments consisting of a protein called tau. 
 These histopathological features in AD are found most commonly in the 
frontal and temporal cortex, hippocampus, and basal forebrain.  Idiopathic 
PD is a movement disorder associated with loss of dopamine containing 
neurons in the substantia nigra of the brain.  Now while these two 
disorders may seem completely separate, there is a significant percentage 
of PD patients who develop dementia and significant percentage of AD 
patients who develop Parkinsonian-like movement disorders.   While it is 
unclear just how much these disorders overlap, I’ve seen figures as high as 
40%.  However, a person with PD who develops dementia may not have AD and a 
person with AD who develops movement disorder may not have PD.  This is 
because there are several different types of dementia, other than AD, which 
result in a continuum of clinical and pathological profiles, thus resulting 
in difficult or mis-diagnoses.  One example is known as Dementia with Lewy 
Bodies (DLB).  Lewy bodies are large intracellular inclusions and have 
historically been associated with the histopathological features found in 
PD.  However, in the 1970’s, reports began to be published where these same 
Lewy bodies were found in the brains of patients who had been diagnosed 
with AD.  As more and more of these cases came to light, it became known as 
Lewy body variant AD.  Just within the past couple of years, more detailed 
clinical and pathological data has been acquired, and now DLB is considered 
by many to be a separate disorder. 
	As far as your question concerning the causes of AD and PD, if I 
could answer that question, I would be on my way to Oslo.  No one knows the 
actual cause of these disorders, probably because there are several 
different etiologies which result in AD or PD.  But, that doesn’t stop 
researchers from trying to find the answers.  Most research in AD focuses 
on the amyloid component of SP.  The amyloid deposited in SP (known as 
beta-amyloid) is part of a larger protein of unknown function, called 
amyloid precursor protein, which, in AD, is not processed in its normal 
way, leading to an accumulation of beta-amyloid.  Many researchers believe 
that this accumulation causes the neuronal cell death and synaptic loss 
associated with AD.  Other researchers focus on the NFTs, which are made up 
of hyperphosphorylated tau, which is a microtubule-associated protein.  
Microtubules are necessary for the intracellular transport of proteins from 
the neuron cell body to the synapse.  These researchers believe that these 
NFTs are the cause of cell death and synapse loss.  Who’s right?  Who 
knows.  To complicate matters, people with trisomy 21 (Down’s syndrome) 
develop dementia as they age and their brains contain loads of SPs but no 
NFTs.  On the other hand, another dementia, known as Pick’s disease is 
marked by hyperphosphorylated tau (in the form of Pick bodies) but no SPs. 
 By now, you should be getting an appreciation of the difficulty in this 
field.
	Likewise, as with AD, no one knows what causes the dopaminergic 
neurons of the substantia nigra to degenerate in PD.  One idea, which is 
gaining in popularity, is that it may be environmental.  There are several 
lines of evidence.  Anecdotal evidence suggests that PD was unknown before 
the 18th century and the industrial revolution.  Further, an outbreak of PD 
or a PD-like disorder was seen several years following the great influenza 
outbreak at the beginning of this century.  More recently, PD was found in 
a group of drug abusers who had made their own amphetamine, but which 
contained a toxin known as MPTP, which caused dopaminergic degeneration.
	Alterations in mitochondrial function has been suggested as a 
possible cause or mechanism of PD, and to a lesser extent AD.  Genetic 
causes are still being examined.  Only about 5% of AD cases appear to be 
familial.  Of these cases, several different genetic loci have been 
implicated, and two genes, presenelin-1 and presenelin-2, have been cloned, 
but their exact function and relation to AD have yet to be determined.  A 
recent study has cloned a gene associated with one extended family of PD 
patients, but its function is also unknown.  More evidence exists for 
mitochondria gene mutations in PD, and this remains an active area of 
interest.