Alzheimer’s disease (AD) brains have two characteristic findings: senile plaques and neurofibulary tangles. While the complete mechanism of AD is unknown, the plaques– aggregations of beta-amyloid proteins and glial cells — are at the very least diagnostically significant.
The plaques and the tangles eventually cause gross atrophy in particular anatomic regions:
Definitive diagnosis, though, requires an invasive biopsy. As such, histology is usually done postmortem and yields slides like this:
AD plaques. Note the globular structures in the middle and on top.
Atrophy is only obvious in late-stage AD and functional differences are suggestive at best. It’d be great if we could florescently tag proteins/genes in brains like we can everywhere else in the body. Unfortunately, brains are typically off-limits due to the blood-brain barrier (BBB).
Harvard researchers, though, decided to try anyways. They attached a MRI probe to a short DNA sequence that is complemtary to a protein expressed in glial cells (the same kind of cells that aggregate around the plaques in AD are made of) and eyedropped it into rats. They then injured the rats via puncture wound and/or stroke to bypass the BBB and induce glial cell localization. Low and behold, the MRIs effectively reported a biopsy confirmed aggregation of glial cells.
It’d be interesting for them to try it with a beta-amyloid DNA sequence attached to the probe. Their methodology could prove useful in the early detection of AD (and other diseases) provided they find a way to bypass the BBB without injuring people.
R. Douglas Fields has an article in March’s Scientific American that reviews his research findings over the past few years and makes an interesting case for the importance of previously ignored white matter in brain processes. The difference between white matter and gray matter is that white matter is primarily composed of myelinated axons while gray matter is composed of the cell bodies that do the information processing. White matter has a lot to do with coordinating how disparate brain regions communicate with each other. His findings, which utilize a new imaging technique called diffusion tensor imaging (DTI), suggest that white matter development and malformation directly affect learning and mental illness.
Few axons are covered with myelin at birth. More are insulated over time, from the back of the cerbral cortex to the front… Basic functional areas such as vision (back) are completed before age 4, followed by language and, last, self-control (forehead).
Doctors have always wondered why schizophrenia typically develops during adolescence[…] this is when the forebrain is being myelinated. The neurons there have largely been established, but the myelin is changing, making it suspect. In addition, nearly 20 studies in recent years have concluded that white matter is abnormal in several regions of the schizophrenic brain. And when gene chips – tiny diagnostic devices that can survey thousands of genes at a time – recently became available, researchers were startled to discover that many of the mutated genes linked to schizophrenia were involved in myelin formation.
The question remains whether or not these findings result in abnormal processing or vise versa. Either way, the article certainly piqued my interest. There are an estimated 10 – 15 times more glia than neurons. It seems reasonable that a malfunction in the neural support system may have important psychological effects.