2011/10/05
A new study attributes infectivity to Alzheimer's disease
- It is still premature to conclude that this type of senile dementia is infectious as, for example, HIV or prion diseases, but indications of its possible infectivity have been found.
- The study, which was published on 4 October in the digital version of the journal Molecular Psychiatry, has been performed in collaboration with researchers of the University of Texas and CIC bioGUNE.
- 'These findings will help us understand the molecular mechanisms implicated in the initiation of Alzheimer's disease and could contribute to the development of new strategies for the prevention and intervention of this type of diseases', said Dr. Castilla, of CIC bioGUNE.
(Bilbao, October 2011).- It is still extremely premature to conclude that Alzheimer's disease has an infective nature, as other diseases like HIV or transmissible spongiform diseases, like the "mad cow disease" or Creutzfeldt-Jacob disease.
Although it is premature, this idea is starting to gain support. New clues have started to appear redirecting the attention of the scientific community in this way, that is, the possible infectivity of Alzheimer's disease, as in the recent case study published in the digital version of the journal Molecular Psychiatry -belonging to the Nature Publishing Group-, a research project led by Dr. Claudio Soto of the University of Texas, and Dr. Joaquín Castilla, Ikerbasque researcher at the Center for Cooperative Research in Biosciences, CIC bioGUNE, in Bilbao.
Alzheimer's disease, the most common type of senile dementia, is associated to the build-up of misfolded peptide in the brain, called amyloid β (Aβ). Although compelling evidences indicate that the misfolding and oligomerisation (subsequent formation of small accumulations to the aforementioned peptide) is the triggering event in Alzheimer's disease, the molecular mechanisms responsible for the initiation of this accumulation are unknown.
The study, conducted on lab mice, by Dr. Soto and Dr. Castilla has shed some more light on the matter by demonstrating that some cerebral anomalies related to Alzheimer's disease can be related to infectious diseases, sharing processes similar to transmissible spongiform diseases, also known as prion diseases, as in the case of the 'mad cow' disease (Creutzfeldt-Jacob disease), etc. With this study a further step has been made to understand this disease, although it is still too premature to conclude that Alzheimer's disease is infectious.
"Our results suggest that some brain anomalies related to Alzheimer's disease could be induced by similar transmission mechanisms to those found in transmissible spongiform diseases, known as prion diseases", confirms Dr. Castilla.
As Dr. Joaquín Castilla explains, formation of Aβ deposits or amyloid plaques could be induced in healthy animals by injecting brain extracts from Alzheimer patients. In this project they were able to observe that the accumulation of amyloid deposits increased progressively with time, after inoculating lab mice. Characteristic AD lesions were observed in brain areas far from the injection site.
'These findings will help us understand the molecular mechanisms implicated in the initiation of Alzheimer's disease and could contribute to the development of new strategies for the prevention and intervention of this type of diseases', said Dr. Castilla.
Now, the question is knowing where the similarities and differences between both processes lie and where the definition of an infectious disease begins and where it ends.
'The main problem - says Dr, Castilla - in classifying Alzheimer's disease as an infectious disease lies in the lack of appropriate models to reproduce each and every one of the pathogenic processes of this disease. Although we have proven that the main event, that is, the formation of amyloid plaques can be produced artificially in a way that reminds us of prion diseases, to extrapolate this data and affirm that Alzheimer's is an infectious disease is still very premature'.
In short, despite the fact that these studies show that the amyloid peptide replicates similarly to an infectious prion, causing the aforementioned diseases, the lack of pathology observed in inoculated animals - mice -, 'its more than doubtful transmission capacity makes us doubt the practical infectivity, and not only theoretic, of Alzheimer's disease', concluded Dr. Castilla.
The discovery of prions and their inclusion in the group of infectious agents forced a reconsideration of the concept of infection itself. 'While no one doubts that replication of the HIV virus in lymphoid cells of an individual represents a clear example of an infectious process, the replication of a single protein or peptide - as in Alzheimer's disease -, does not meet all the characteristics that we are used to finding in the definition of infection', says Castilla.
Figure. Human wild-type amyloid precursor protein (APP) gene (HuAPPwt) mice inoculated with Alzheimer's disease (AD) brain extracts develop cerebral amyloid-β (Aβ) deposits. (a) HuAPPwt mice injected with brain homogenates from a healthy individual (left panel) or an AD patient (middle and right panels) were killed at different times after injection. Brain slides were stained with anti-Aβ (4G8) antibody (left and middle panels) or Thioflavin S (ThioS; right panels). Pictures correspond to representative slides of all animals analyzed. Arrows point to Aβ deposits typically observed in the inoculated mice. (b) Representative slides of the hippocampus of three different mice killed 30 days-post injection (dpi), where no Aβ deposits were detected by immunohistochemistry (4G8). Similar results were obtained in animals killed 90 dpi (data not shown). Picture magnification is indicated in the bottom-left corner.
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