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.
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.
| 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).
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).
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.
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.
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.
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.
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| RodrigoMedeiros.com |
Alzheimer's Disease Research
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