Amyloid plaques
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are
History
In 1892, Paul Blocq and Gheorghe Marinescu first described the presence of plaques in grey matter.[8][9] They referred to the plaques as 'nodules of neuroglial sclerosis'. In 1898, Emil Redlich reported plaques in three patients, two of whom had clinically verified dementia.[10] Redlich used the term 'miliary sclerosis' to describe plaques because he thought they resembled millet seeds, and he was the first to refer to the lesions as 'plaques'.[4]
In the early 20th century,
In 1911, Teofil Simchowicz introduced the term 'senile plaques' to denote their frequent presence in the brains of older individuals.[15][16][17] In 1968, a quantitative analysis confirmed the association of senile plaques with dementia.[18] The term 'neuritic plaques' was used in 1973 to designate plaques that include abnormal neuronal processes (neurites).[19] An advance in 1984 and 1985 was the identification of Aβ as the protein that forms the cores of plaques.[20] This discovery led to the generation of new tools to study plaques, particularly antibodies to Aβ, and presented a molecular target for the development of potential therapies for Alzheimer's disease.[4][21][22][23]
The generation of amyloid beta
Amyloid beta (Aβ) is a small protein, most often 40 or 42 amino acids in length, that is released from a longer parent protein called the Aβ-precursor protein (APP).[24] APP is produced by many types of cell in the body, but it is especially abundant in neurons. It is a single-pass transmembrane protein, passing once through cellular membranes.[25]
The Aβ segment of APP is partly within the membrane and partly outside of the membrane. To liberate Aβ, APP is sequentially cleaved by two
Identification
Amyloid plaques are visible with the
Composition
The Aβ deposits that comprise amyloid plaques are variable in size and appearance.
Anatomical distribution
Dietmar Thal and his colleagues have proposed a sequence of stages of plaque formation in the brains of Alzheimer patients[34][35] In Phase 1, plaques appear in the neocortex; in Phase 2, they appear in the allocortex, hippocampal formation and amygdala; in Phase 3, the basal ganglia and diencephalon are affected; in Phase 4, plaques appear in the midbrain and medulla oblongata; and in Phase 5, they appear in the pons and cerebellum. Thus, in end-stage Alzheimer's disease, plaques can be found in most parts of the brain. They are uncommon in the spinal cord.[4]
Formation and spread
The normal function of Aβ is not certain, but plaques arise when the protein misfolds and begins to accumulate in the brain by a process of molecular templating ('seeding').
Involvement in disease
Abundant Aβ plaques, along with
The diagnosis of Alzheimer's disease typically requires a microscopic analysis of plaques and tangles in brain tissue, usually at autopsy.
Occurrence
The probability of having plaques in the brain increases with advancing age.[44] From the age of 60 years (10%) to the age of 80 years (60%), the proportion of people with senile plaques increases linearly. Women are slightly more likely to have plaques than are men.[45][44] Both plaques and Alzheimer's disease also are more common in aging persons with trisomy-21 (Down syndrome).[1][46] This is thought to result from the excess production of Aβ because the APP gene is on chromosome 21, which exists as three copies in Down syndrome.[46]
Amyloid plaques naturally occur in the aging brains of nonhuman species ranging from birds to great apes.[4] In nonhuman primates, which are the closest biological relatives of humans, plaques have been found in all species examined thus far.[47] Neurofibrillary tangles are rare, however, and no nonhuman species has been shown to have dementia along with the complete neuropathology of Alzheimer's disease.[48]
Research
Both human samples and
The environmental, physiological or genetic risk factors for plaque formation in Alzheimer's disease are under preliminary research.[53][54]
See also
- Prion
- Proteopathy
References
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