It has been shown that the degree of cognitive impairment in diseases such as AD is significantly correlated with the presence of<unk> s. Harmful or protective? There has been some suggestion that the formation of<unk> s does not have a causal relationship with disease. Rather that<unk> s may be produced in response to a variety of conditions and may in fact be a compensatory response against oxidative stress and serves a protective function. Several points are made to argue the position that<unk> s are perhaps protective instead of harmful. First there appears to be a dispute as to the impact of<unk> s on neuronal viability because some neurons containing<unk> s survive for decades. Furthermore,<unk> s have been found in apparently healthy individuals, indicating that<unk> s are not directly related to neural degeneration. It has been proposed that the formation of<unk> s is part of a multifaceted compensatory response where oxidative insult activates several kinases, which are then capable of phosphorylating tau. This then prompts the early formation of<unk> s, which reduce oxidative damage and prolong the function of the neuron. While the theory is intriguing, scientists have not come to a firm conclusion as to what role<unk> s play in neurodegenerative diseases. Results from the new study suggest that a specific phosphorylation of tau (at threonine-205) has a protective effect on neurons in a mouse model of excitotoxic, amyloid beta toxicity. The authors suggest that the reason tau becomes modified is to protect from damage caused by amyloid protein aggregation. A protein called kinase p38γ phosphorylates tau at the threonine-205 amino acid. The activity of this gamma kinase enzyme is mostly lost as Alzheimer Disease progresses, suggesting a loss of this protective effect. Reintroducing p38γ and increasing its activity prevented memory deficits from occurring in their mouse model, suggesting this enzyme as a potential target for future therapies. However increasing the activity of kinases has been shown to be difficult). Neuron loss Traditionally believed to play a major role in neuron loss,<unk> s are an early event in pathologies such as Alzheimer's disease, and as more<unk> s form, there is substantially more neuron loss. However, it has been shown that there is significant neuron loss before the formation of<unk> s, and that<unk> s account for only a small proportion (around 8.1%) of this neuron loss. Coupled with the longevity of neurons containing<unk> s, it is likely that some other factor is primarily responsible for the bulk of neuron loss in these diseases, not the formation of<unk> s. Primary age-related tauopathy vs. classical Alzheimer's It is currently unclear as to whether or not primary age-related tauopathy (PART), a term which includes some cases formerly referred to as<unk> -predominant dementia <unk> PD) or<unk> -only dementia, is a variant of the traditional Alzheimer's disease, or a distinct entity. Characterized by later onset and milder cognitive impairment, the distribution of<unk>  pathology is more closely related to that found in centenarians showing no or limited cognitive impairment.<unk> s are generally limited to allocortical/limbic regions of the brain with limited progression to the neocortex but a greater density in the allocortical/hippocampal region. Plaques are generally absent. Alzheimer disease with concomitant dementia with Lewy bodies (AD+DLB) The degree of<unk>  involvement in AD is defined by Braak staging. Braak stages I and II are used when<unk>  involvement is confined mainly to the transentorhinal region of the brain. Stages III and IV are indicated when there is involvement of limbic regions such as the hippocampus, and V and VI when there's extensive neocortical involvement. This should not be confused with the degree of senile plaque involvement, which progresses differently.<unk>  and modified Braak scores were lower in AD+DLB, however, neocortical<unk>  scores show markedly different patterns between AD+DLB and Classical Alzheimer's. In pure AD,<unk>  are predominantly found at a high frequency: In AD+DLB, the distribution of<unk>  frequency was found to be bimodal:<unk> s were either frequent or few to absent. Additionally, neocortical<unk>  frequency in the AD+DLB group tended to parallel the severity of other types of tau cytopathology. Link to aggression and depression in people living with Alzheimer's disease A recent study looked for correlation between the quantitative aspects of Alzheimer's disease (neuron loss, neuritic plaque and<unk>  load) and aggression frequently found in Alzheimer's patients. It was found that only an increase in<unk>  load was associated with severity of aggression and chronic aggression in Alzheimer's patients. While this study does indicate a correlation between<unk>  load and severity of aggression, it does not provide a causative argument. Research has also indicated that patients with AD and comorbid depression show higher levels of<unk>  formation than individuals with AD but no depression. Comorbid depression increased the odds for advanced neuropathologic disease stage even when controlling for age, gender, education and cognitive function.
Neurofibrillary tangle
Amyloid plaques
Geographic atrophy
Superficial siderosis
Microinfarct
Lewy body
Wallerian degeneration
Hippocampal sclerosis