Vaccines : Alzheimer's Disease
Alzheimer's disease ( AD ) is a progressive degenerative brain disease - is the most common form of dementia. Dementia – in simple words – is the loss of intellectual and social abilities.
Most of the research in this field is done in the USA, which shows that presently more than 4 million Americans suffer from AD. This figure is expected to go up more than thrice – to about 14 million – within 20 years. Although until now there is no definitive treatment or prevention for AD, tremendous progress has been made recently in this field.
Ronald Reagan, once the president of the US and the person who defused the cold
war by initiating the START I and START II treaties, has Alzheimer's. He no
longer remembers his wife's name or recognizes who she is.
I don't know anything about Alzheimer's!
1) Genetic :
Chromosomes 1, 14, 19 and 21(trisomy) being incriminated,
is diffuse cerebral atrophy with widening of cerebral sulci – the occipital
lobes being spared in most cases. There is compensatory ventricular
enlargement (hydrocephalus ex vacuo).
In Alzheimer's deposition of amyloid in the brain is found in a typical plaque which is known as a senile plaque. A closer look at the amyloid in these plaques is warranted, since it is the basis for the vaccine under development.
Image : Please click on the image to view a bigger, clearer image with a short description.
The beta peptide is a fragment of a much larger
amyloid precursor protein (beta-APP), the normal function and source
of which are not yet known.
So... How does the vaccine work??
The vaccine for AD is made up of a fragment of the amyloid
precursor protein (APP) – which is deposited as senile plaques, as
From the knowledge gathered from the animal models so far, the mechanism of working of the vaccine is as follows –
Although, predominantly it is humoral immunity, but a role of cell mediated immunity cannot be ruled out as well.
Thus, the widespread amyloid deposition, activation of microglia and presence of NFT in AD might be amenable to a therapeutic vaccination stratagem that is designed to prevent the deposition of beta amyloid peptide in plaques or tau in NFT in the first place or, once present, to rid the brain parenchyma of extracellular amyloid and intracellular NFT.
Some Caveats :
***The exact immunomodulators involved in this process
have not been found out as yet. For example, circulating, local and
plaque-bound cytokines, chemokines, compliment and compliment inhibitors have
not been well studied in any of the animal models.
Role of the vaccine :
Although the exact cause of AD still remains elusive, the vaccine developed against AD is directed against preventing, delaying or reversing the formation of AD-associated lesions. Recent results, using the transgenic mouse model, have suggested that immunological interventions can retard and even reverse the development of at least some of the pathological changes of AD, and thus alleviate the symptoms associated with the disease.
- Mukesh Sharma
Besides senile plaques, two other abnormalities are noticed in the microscopic sections of most Alz-affected brains :
Image : The arrow points to a neurofibrillary tangle. Please click on the image to view a larger version
Image : Amyloid angiopathy and diffuse plaques of amyloid . Please click on image to view a larger version.