Aluminium and Alzheimer's disease Dr Subhash Donde

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Aluminium Is it a risk factor for Alzheimers
Disease?

• Dr. Subhash Donde
• Dept. of Zoology, Kirti College, Dadar,Mumbai-400
  028.

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Dr. Alois Alzheimer
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Alzheimers disease Statistics

• 25 million sufferer all over world
• 75 million at risk of developing AD in next 20-25
  years
• Age wise prevalence of AD
• 1 prevalence at age of 60-64 years
• 50 prevalence at age of 90 years and above

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• The avg. annual cost per person with AD
• ranges from 15,000 to 50,000
• (USA, EU, Japan)
• Lifetime cost per patient over 175,000
• 15-20 of total cost is meant for treatment
• while rest is for nursing/caring patients.
• Who suffer more -the patient or the family?
• 200 compounds tested during last decade

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Brain of normal and Alzheimer patient lateral
view
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(No Transcript)
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• AD is a multifactorial, polygenic disease. 5000
  research papers world-wide in last 20 years
  documented genetic basis of the disease.
• 10 different genes associated with AD and more
  than 50 genes involved in dementia
  (www.ncbi.nlm.nih.gov)
• Environmental factors such as Aluminium is also
  strongly linked with AD

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• Some heavy metals induced neurodegenerative
  diseases
• Manganese Parkinsonism
• Lead Acute encephalopathy and severe mental
  retardation
• Aluminium
• 1 Microcytic anemia
• 2 Ostemalacia
• 3 Encephalopathy
• 4 Amyotrophic Lateral Sclerosis (ALS)/ Sporadic
  motor neuron disease
• 5 Alzheimer's disease (AD)

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• Aluminium neurotoxicity Historical account
• Dolken (1897) produced neuronal degeneration in
• rabbits brain by injecting aluminium tartarate
• Klatzo (1965) produced same results as above
• Crapper (1973) repeated above results in cats
  brain.
• Wisniewski and Wen (1992) reported
  dissimilarities
• in senile plaques and NFTs found in AD brain and
  those
• produced in aluminium treated animals.
• Landsberg (1992) opined that Al found in senile
• plaques might have originated as contamination of
  dyes
• used to stain plaques.
• Savory (1995) and other reported similarities in
  
• immunochemical ultra structural hallmarks of AD
  brain
• And aluminium treated animal models and cultured
  
• neurons

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Extra cellular senile plaques and intraneural
NFTs in AD brain
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AD and Al-induced animal model of AD Similarities

• Hallmark of Brain of Alzheimers patient
• Extra cellular senile plaques (ß amyloid protein)
• Intraneural neurofibrillary tangles
  (phoshorylated tau protein)
• Degeneration of synapses and neurons

• Al-induced AD model / cultured neuron
• Aluminium caused neurofibrillary degeneration
• Presence of PAH and immunoreactivity for tau
  protein
• Neuronal death and degeneration of synapses

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Role of tau protein in microtubule formation
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Abnormal hyperphosphorylation of tau protein
and formation of NFTs in Alzheimer brain
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• Sources of Aluminium exposure
• Drinking water(Aluminium sulphate- flocculent)
• Leaching through utensils (low grade Al-Pb
• Alloy)
• Tea
• Antacids (Aluminium hydroxide)
• Antiperspirants (Aluminium chorohydrate)
• Occupational exposure (mining/smelting)
• (aluminium dust or fumes)

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• Concluding Remarks
• Neurotoxicity of aluminium is well established in
• connection with Alzheimers disease.
• Hence following steps need to be taken in order
  to
• Avoid lifetime exposure of aluminium
• Low grade aluminum vessels should be replaced
• with either coated or high grade alloys of
  aluminium
• Cooking acidic food in Al vessels should be
  avoided
• Aluminium based antacids should be replaced by
• another harmless preparation
• Use of antiperspirant should be kept at minimum.

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Brain of (A) normal and (B) Alzheimer patient
(note enlarged sulci)
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View of brain within cranium (note overall
shrinkage in brain due to neuronal death)
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PETscan of brain of normal and AD patient (Arrow
points to areas with dead neurons)
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Thanks !