Diagram of how microtubules disintegrate with Alzheimer's disease Mutated tau The traditional understanding is that tau binds to microtubules and assists with their self-assembly, formation and stabilization. However, when tau is hyperphosphorylated, it is unable to bind and the microtubules become unstable and begin disintegrating. The unbound tau clumps together in formations called<unk> s. More explicitly, intracellular lesions known as pretangles develop when tau is phosphorylated excessively and on improper amino acid residues. These lesions, over time, develop into filamentous interneuronal<unk> s <unk> s) which interfere with numerous intracellular functions. Seeking a reliable animal model for tau-related pathologies, researchers expressed the human mutant P301L tau gene in adult mice. This experiment resulted in the formation of<unk> s and pretangle formations. The human mutant P301 tau gene is associated with frontotemporal dementia with parkinsonism, another tauopathy associated with<unk> s. It was found that the degree of tau pathology was dependent on time and the level of gene expression. Groups receiving a combination of a promoter and enhancer in the vector saw increased tau expression, as early as 3 weeks after vector injection, which was measured using a Western blot. These groups also showed a greater pathology compared to those with less expression of the mutant tau. Additionally,<unk> s were clearly detected by immunoelectron microscopy at 4 months but not at 2 months. However, at both 2 and 4 months, pretangle-like structures were observed suggesting the<unk>  formation is not complete by 4 months and will continue to progress with time. Traumatic brain injury Preliminary research indicates that iron deposits due to hemorrhaging, following traumatic brain injury (TBI), may increase tau pathology. While TBI does not routinely lead to accelerated<unk>  formation, further work may determine if other blood components or factors unrelated to hemorrhages are involved in this TBI-induced augmentation of tau pathology.<unk> s are most commonly seen associated with repetitive mild TBI as opposed to one instance of severe traumatic brain injury. For example, the neurodegenerative disease chronic traumatic encephalopathy (CTE), previously called dementia pugilistica, is highly associated with<unk> s and neuropil threads. Aluminium The idea that there is a link between aluminium exposure and the formation of<unk> s has floated around the scientific community for some time without having been definitively proved or disregarded. Recently a study examining the hippocampal CA1 cells from individuals with and without Alzheimer's disease showed a small portion of the pyramidal cells contain cytoplasmic pools within their somas containing early<unk> s. These cytoplasmic pools are aggregates of an aluminium/hyperphosphorylated tau complex similar to mature<unk> s. (Walton) While a connection between aluminium and<unk> s and AD is maintained, there is evidence that aluminium does not directly cause the formation of<unk> s or AD. However it is claimed that chronic aluminium intake can cause Alzheimer's by disrupting the microtubules in the filaments.
Neurofibrillary tangle
Amyloid plaques
Geographic atrophy
Superficial siderosis
Microinfarct
Lewy body
Wallerian degeneration
Hippocampal sclerosis