In 1906, Alois Alzheimer gave a lecture at a congress in Tübingen, Germany, on the first case
of the disease that Kraepelin some years later named Alzheimer’s disease (Möller and
Graeber, 1998). In this single case, Alzheimer described typical clinical characteristics with
memory disturbances and instrumental signs, and the neuropathological picture with miliary
bodies (plaques) and dense bundles of fibrils (tangles), which we today know are the
hallmarks of the disease.
of the disease that Kraepelin some years later named Alzheimer’s disease (Möller and
Graeber, 1998). In this single case, Alzheimer described typical clinical characteristics with
memory disturbances and instrumental signs, and the neuropathological picture with miliary
bodies (plaques) and dense bundles of fibrils (tangles), which we today know are the
hallmarks of the disease.
| Alois Alzheimer (1864-1915) |
A diagram of the neurofibrillary
tangles found in August Deter's
brain, from a 1911 research paper
by Alois Alzheimer.
tangles found in August Deter's
brain, from a 1911 research paper
by Alois Alzheimer.
Alzheimer’s disease (AD) is a neurodegenerative disorder that currently affects nearly 2% of
the population in industrialized countries; the risk of AD dramatically increases in
individuals beyond the age of 70 and it is predicted that the incidence of AD will increase
threefold within the next 50 years (www.alz.org). With the expected increase in the
prevalence of AD will come an increase in the financial burden caused by this condition. AD
already takes an enormous financial toll on society; the Alzheimer’s Association and the
National Institute on Aging estimate that the current direct and indirect costs of caring for the
4.5 million Americans with AD are at least $100 billion annually (Mount and Downton, 2006).
the population in industrialized countries; the risk of AD dramatically increases in
individuals beyond the age of 70 and it is predicted that the incidence of AD will increase
threefold within the next 50 years (www.alz.org). With the expected increase in the
prevalence of AD will come an increase in the financial burden caused by this condition. AD
already takes an enormous financial toll on society; the Alzheimer’s Association and the
National Institute on Aging estimate that the current direct and indirect costs of caring for the
4.5 million Americans with AD are at least $100 billion annually (Mount and Downton, 2006).
Brain regions involved in learning and memory processes, including the temporal and frontal
lobes, are reduced in size in AD patients as the result of degeneration of synapses and death
of neurons. Because there can be other causes of memory loss, definitive diagnosis of AD
requires postmortem examination of the brain, which must contain sufficient numbers of
“plaques” and “tangles” to qualify as affected by AD. Plaques are extracellular deposits of
fibrils and amorphous aggregates of β-amyloid (Aβ) peptide; diffuse deposits of Aβ also
present in high amounts. Neurofibrillary tangles are intracellular fibrillar aggregates of the
microtubule-associated protein tau that exhibit hyperphosphorylation and oxidative
modifications.
lobes, are reduced in size in AD patients as the result of degeneration of synapses and death
of neurons. Because there can be other causes of memory loss, definitive diagnosis of AD
requires postmortem examination of the brain, which must contain sufficient numbers of
“plaques” and “tangles” to qualify as affected by AD. Plaques are extracellular deposits of
fibrils and amorphous aggregates of β-amyloid (Aβ) peptide; diffuse deposits of Aβ also
present in high amounts. Neurofibrillary tangles are intracellular fibrillar aggregates of the
microtubule-associated protein tau that exhibit hyperphosphorylation and oxidative
modifications.
Adapted from: American Health Assistance Foundation (http://www.ahaf.org/alzdis/about/AmyloidPlaques.htm) AND Mattson;
Nature, 430:631-639, 2004.
Nature, 430:631-639, 2004.
Besides ageing, which is the most obvious risk factor for the disease, epidemiological studies
have suggested several tentative associations. Some can be linked to a decreased reserve
capacity of the brain, including reduced brain size, low educational and occupational
attainment, low mental ability in early life, and reduced mental and physical activity during
late life. Moreover, several epidemiological studies have shown that head injury could be a
risk factor Other risk factors are associated with vascular disease, including hypertension,
hypercholesterolaemia, atherosclerosis, coronary heart disease, smoking, obesity, and
diabetes.
There are currently two classes of drugs approved for the treatment of symptoms of late-
onset or sporadic AD. Acetylcholinesterase (AChE) inhibitors prolong the action of
acetylcholine in the synapse by preventing its breakdown. This strategy results in
improvements of cognition, mood and behavior. N-methyl-D-aspartate (NMDA) receptor
antagonists are believed to work by helping to regulate levels of the neurotransmitter
glutamate. However, none of the currently approved drugs stops the underlying
degeneration of brain cells or reverses the progression of AD. Drugs are in development that
target specific sites in the neurodegenerative cascade. Because the production of neurotoxic
forms of Aβ from APP appears to be a pivotal event in AD pathogenesis, there is intense
interest in developing drugs that block the β- or γ-secretase enzymes. Another promising
approach for preventing and treating AD is based upon stimulating the immune system to
remove Aβ from the brain.
have suggested several tentative associations. Some can be linked to a decreased reserve
capacity of the brain, including reduced brain size, low educational and occupational
attainment, low mental ability in early life, and reduced mental and physical activity during
late life. Moreover, several epidemiological studies have shown that head injury could be a
risk factor Other risk factors are associated with vascular disease, including hypertension,
hypercholesterolaemia, atherosclerosis, coronary heart disease, smoking, obesity, and
diabetes.
There are currently two classes of drugs approved for the treatment of symptoms of late-
onset or sporadic AD. Acetylcholinesterase (AChE) inhibitors prolong the action of
acetylcholine in the synapse by preventing its breakdown. This strategy results in
improvements of cognition, mood and behavior. N-methyl-D-aspartate (NMDA) receptor
antagonists are believed to work by helping to regulate levels of the neurotransmitter
glutamate. However, none of the currently approved drugs stops the underlying
degeneration of brain cells or reverses the progression of AD. Drugs are in development that
target specific sites in the neurodegenerative cascade. Because the production of neurotoxic
forms of Aβ from APP appears to be a pivotal event in AD pathogenesis, there is intense
interest in developing drugs that block the β- or γ-secretase enzymes. Another promising
approach for preventing and treating AD is based upon stimulating the immune system to
remove Aβ from the brain.
 |
| |
 |
| |
 |
| |
 |
| RodrigoMedeiros.com |
Alzheimer's Disease Research
 |  |  |  |