1. Tau
1.1. Tau PET scan predicted severity of cognitive impairment more precisely than Aß.
1.1.1. GLUT-3 and GLUT-1 decrease was associated with tau
1.1.2. O‐GlcNAcylation The decrease in intraacellular glucose results in decrease of GlcNAcylation and increased tau phosphorylation
1.2. Tau is mildly increased in cognitively normal patients with T2D
1.2.1. Ilustration
1.3. Tau PET scans remarkably correlate with atrophy
1.3.1. Illustration - Violet - Brain atrophy, Green - tau buildup
2. Anti-diabetic drugs in treatment of AD
2.1. Mice and human study proved protective effect of Metformin
2.1.1. Mice study
2.1.1.1. Metformin increased expression of both GLUT-1 and GLUT-3
2.1.2. Human Study
3. Neuroenergetic hypothesis of AD
3.1. Evidence for brain glucose dysregulation in Alzheimer's disease
4. Transporters
4.1. Illustration from a very recent glucose transport review
4.2. GLUT 3
4.2.1. In the study linked to this bubble, it was proven by analysis of postmortem brains that the decrease of GLUT3 and GLUT1 transporters is associated with increase tau phosphorylation, in turn tau PET imaging is emerging marker with better prediction power than amyloid PET
4.2.1.1. Another study showing decrease in GLIT-3 in AD brain. The reduction of GLIT-3 was greater than loss of synapses
4.2.1.2. Even
4.2.2. Responsible for transporting glucose to neurons - GLUT-3 is the main neural glucose transporter
4.2.3. GLUT-3 expression is regulated by hipoxia inducible factor
4.2.3.1. Illustration of a dramatic HIF-1alpha
4.2.3.1.1. Beside inducing GLUT expression, HIF-1 is discussed in the literature for its neuroprotective effects as well
4.2.3.2. Study with details of that mechanism
4.2.4. Dramatic decrease in GLUT-3 but not GLUT-1 was detected in T2D patients. With no difference in HIF-1alpha
4.2.4.1. Illustration
4.2.5. GLUT 3 was thought to be insulin independent but it was found that the translation onto the membrane (uemura and greenlee, 2006)
4.3. GLUT 1
4.3.1. https://www.frontiersin.org/articles/10.3389/fnins.2020.00668/full#B21
4.3.2. Responsible for transporting glucose from blood across the BBB, astrocytes are also using mostly GLUT1 for both inlux and efflux of glucose
4.3.2.1. Incretin GLP-1 was able to restore the transfer of glucose across BBB
4.3.2.2. Importance of GLUT-1
4.3.2.3. Decrease of GLUT1 correlated with AD severity in mice
4.3.2.4. In mice, omega 3 deficiency is associated with decreased glucose transport and density of GLUT 1 in the BBB
4.4. GLUT2
4.4.1. Unlike GLUTs 1&3, GLUT2 levels are increased in AD brains