Primary antibodies for the neurobiology area include the ever popular anti-Iba1 (ionised calcium binding adaptor molecule 1),
a marker for macrophages and microglia often used in brain research.
The median age of the UK population is rising. This ageing society brings an increase in age associated diseases such as dementia, and research into these conditions is likewise drawing greater attention. Alpha Laboratories offer a number of products that may be used in the investigation of brain pathology when researching Alzheimer's, Parkinson's or other neurological conditions.
Alzheimer’s disease is the most common cause of dementia, typically affecting those over 65 years of age although the less common early-onset Alzheimer’s can take hold much earlier. During the progression of the disease protein plaques and neurofibrilllary tangles develop in the brain.
The senile plaques that occur are dense, insoluable deposits of amyloid-beta (A-beta) peptide and other material which accumulate outside and around neurons. A-beta peptide can exist in both 40 and 42 amino acid forms. A-beta 42 aggregates more readily than the 40 amino acid peptide and it is A-beta 42 that is initially deposited. Early stage, diffuse plaques may be A-beta 42 positive but A-beta 40 negative. Plaques containing the A-beta 40 may only appear in the more advanced stages of disease.
Neurofibrillary tangles are the result of protein aggregation within the cell. The neuron cytoskeleton is a supporting structure made up of microtubles which serve to guide molecules between the body of the cell to the end the axon. The microtube-associated protein Tau becomes hyperphosphorylated and then aggregates with other threads producing neurofibril tangles and disrupting the neuron’s transport system.
Parkinson’s Disease is a neurodegenerative disorder characterised by cell loss within the substantia nigra and symptoms of bradykinesia, rigidity and tremor. Parkinson’s effects 1 in every 500 people in the UK and further work is required to understand the disease and develop new therapies. One of the pathological hallmarks of this disease is the presence of protein aggregates called lewy bodies, although these are also seen in other conditions such as dementia with lewy bodies
The ubiquitin-proteasome system serves to removes unwanted proteins that are no longer required by the cell. Dysfunction of this system results in a build of up proteins, including alpha-synucein which is a major component of the lewy bodies that characterise Parkinson’s. Lewy bodies are alpha-synuclein-immunoreactive inclusions comprising a number of neurofilament proteins together with proteins responsible for proteolysis. One of the first sites for deposition of lewy bodies is the olfactory bulb. Involvement of the substantia nigra areas of the midbrain and basal forebrain occurs later as the disease progresses and eventually the neocortex is affected.
Alpha Synuclein Modification
Whilst the mechanisms of alpha-synuclein aggregation are still not fully understood, it appears that much of the alpha-synuclein found in lewy bodies is phosphorylated and that phosphorylation may influence cell toxicity. Phosphorylated alpha –synuclein may therefore be of key importance in the progression of this disease.
Neurodegenerative diseases are often associated with reduced levels of specific neurotransmitters. Cholinergic transmission is impaired in Alzheimer’s disease; in particular the cholinergic neurons of the basal forebrain which project into the cortex are affected. In dementia with Lewy bodies it is the cholinergic projections from the brain stem to the thalamus that appear to be impaired. Levels of the both the neurotransmitter acetylcholine (ACh) andacetylcholine esterase (AChE) an enzyme which degrades ACh are reduced in individuals with dementia.
In Parkinson’s disease the main neurotransmitter of interest is dopamine, it is the death of dopamine producing nerve cells in the brain stem that help characterise this disease. Dopamine stimulates motor neurons involved in movement and patients may have lost 80% of their dopamine neurons by the time symptoms appear.
Ionized calcium-binding adapter molecule 1(IBA-1) protein is a calcium binding protein specifically expressed in macrophages and microglia. IBA-1 may also be another name for the microglial marker, allograft inflammatory factor -1 (AIF-1) as it is possible that these are the same protein. The expression of IBA-1 is associated with the actin cytoskeleton and is upregulated in microglial cells following brain injuries and diseases. As such IBA-1 may be involved in signal transduction and recruitment of cells during the inflammatory process. Whilst the purpose of infiltrating macrophages and microglia to the inflammatory site is to phagocytose pathogens and debris, microglia may also contribute to some neurodegenerative diseases as a result of cytotoxic molecule and pro-inflammatory cytokine production.
Options for immunohistochemistry and Western blotting Anti-Iba1 antibodies are available, offering no cross-reactivity with astrocytes.
Antibodies to detect other marker molecules including olfactory protein, phosphorylated α-synuclein, Syntaxin, Amyloid β peptide and Acetylcholinesterase are also available.