The document discusses the complexities of diagnosing Alzheimer's disease, emphasizing that a definitive diagnosis can only occur postmortem through autopsy due to the identification of specific biological markers. While alive, psychological symptoms and certain proteins found in cerebrospinal fluid can provide clues, but they are not exclusive to Alzheimer’s. Additionally, it describes methodologies for studying behavioral changes in transgenic mice models using techniques like immunostaining and wet mazes.

1. Anna LysenkoAlzheimer’s Disease

2. DiagnosisIt is very important to understand that a final diagnosis cannot be made until the person is deceased, in a postmortem autopsy report. The reason for this is that to make a medical diagnosis, a medical examiner needs to be able to identify certain biological markers that are solely identifiable within the diseasethese identifiers are mainly amyloid plaque build ups and neurofibrillary tangles which are present in the brain (Allan, Sexton, Welchew & Ebmeier, 2009).

3. Diagnosis While AliveWhile person is still living, you can examine psychological symptoms as well as a few biological markers but they are not unique to AD. The most common ones are total tau protein, phosphorylated tau protein, and amyloid beta 1-42 protein, these proteins are tested and extracted from the cerebrospinal fluid through a procedure called the spinal tapT-tau and P-tau levels are typically increased while Aβ-42 is decreased in Alzheimer’s patients.

4. Immunostaining for Confocal MicroscopyBrain sections of control mice are taken and stained with antibodies Ki67, which is an antibody that stains for proliferating cells, and Doublecortin (DCX), which stains for immature neurons, and studied under the Confocal microscope (which uses different fluorescent wave length to fluoresce specimens that were stained by antibodies).

5. Control mouse

6. Transgenic mouse

7. Immunostaining for light microscopyBrain sections can also be studied under a light microscope in order to see the plaque build up in mice at different stages of the disease.

8. Amyloid plaque build up in a 3 month old transgenic mouse brain

9. Amyloid plaque build up in hippocampus of a 28 month old transgenic mouse

10. Neuronal differencesThe periventricular zone of the brain as well as the dentate gyrus of the hippocampus show a significant number of proliferating cells as well as immature neurons, with processes that extend throughout the granular layer of the hippocampus. Some cells test positive for both. When it comes to mice which are transgenic the number is significantly decreased. Mainly in hippocampus, differences in dentate gyrus are insignificant.

11. Behavioral TestsWet mazes are a very common technique in which a mouse is places into a tub of opaque water and is then expected to swim toward an acrylic platform visible slightly above the surface of the water which the mouse must stand on in order to get out of the water. After a few tries the platform is hidden under the surface of the water but the mouse is eventually able to learn and memorize where it is so that it can stand on it.

12. Wet Maze