Amyloid Deposits in Brains of Non-Alzheimer’s Individuals | Amprion

Amyloid Deposits in Brains of Non-Alzheimer’s Individuals

By March 30, 2018 No Comments

Originally Posted on Acta Neuropathologica Communications | 18 November 2013

scientist studying Amyloid Deposits

Background: One of the main features of Alzheimer’s disease (AD) is the presence of Aβ Amyloid-b deposition in brains, which accumulate in the brain years before the onset of symptoms. We and others have demonstrated that cerebral Aβ-amyloidosis can be induced in vivo by administration of AD-brain extracts into transgenic mice. However, it is currently unknown whether amyloid formation can be induced using extracts from individuals harboring Aβ deposits, but not clinical disease.

Results: In this study we analyzed the amyloid-inducing capability of samples from individuals affected by mild cognitive impairment (MCI) and Non-Demented persons with Alzheimer’s disease Neuropathology (NDAN). Our results show that inoculation of transgenic mice with MCI and NDAN brain samples accelerated Aβ pathology in a similar way as extracts from confirmed AD.

Conclusions: This data demonstrate that the sole presence of Aβ aggregates in a given sample, regardless of the clinical condition, is capable to accelerate Aβ deposition in vivo. These findings indicate that the amyloid-inducing activity may be present in the brain of people during pre-symptomatic or a-symptomatic stages of AD.

Background on Amyloid Deposits

Alzheimer’s disease (AD) is a prevalent brain disorder, mostly affecting individuals over 65 years old. Clinically, this progressive and irreversible neurodegenerative illness is characterized by cognitive decline, which invariably leads to dementia. The hallmark neuro-pathological lesions of AD brain are the extracellular deposition of misfolded amyloid-β (Aβ) as amyloid plaques and the formation of neurofibrillary tangles composed by intracellular aggregates of hyper-phosphorylated tau. Aβ aggregates in AD can be found in a variety of arrangements such as soluble Aβ oligomers, diffuse deposits, dense core senile plaques, vacular deposits, and intra-cellular aggregates, among others. To different degree, all these structures have been associated to cell toxicity and tissue dysfunction.

Accumulation of Aβ aggregates in the brain is thought to begin many years or even decades before the onset of AD clinical symptoms. Indeed, abundant amounts of Aβ deposits are detected in the brain of some subjects affected by mild cognitive impairment (MCI), which is considered a precursor stage of AD. Most patients with amnestic MCI do not meet the full neuropathologic criteria for AD, but their pathological features suggest a transitional state evolving towards AD. MCI is a clinical condition usually defined by subtle memory changes that do not significantly affect daily life. MCI does not meet diagnostic criteria for dementia; however, people affected by this condition are at high risk to convert into AD.

Alternatively, it is widely known that elderly people usually exhibit cerebral Aβ pathology, even without any signs of dementia. In fact, it is not uncommon to find cases of aged non-demented subjects harboring abundant amyloid lesions in their brains (here referred as Non-Demented individuals with Alzheimer’s disease Neuropathology or NDAN). These cases suggest that certain arrangements of misfolded Aβ are not associated to a clinical phenotype or that some people can cope with accumulation of misfolded aggregates.

Recent studies have demonstrated that inoculation of AD brain homogenates is able to accelerate amyloid de-position in AD-transgenic mice. Furthermore, AD samples are also able to induce de novo Aβ pathology in animal models that do not spontaneously develop this type of lesions during their whole lifespan. These findings suggest that the accumulation of Aβ deposits follows a seeding-dependent process of misfolding and aggregation that can be induced in a prion-like manner by administration of preformed aggregates. Experimental induction of amyloid pathology has been achieved by injection of brain samples from AD patients and aged AD-transgenic mice.

However, there are no reported studies investigating whether the pathological induction can also be observed upon inoculation of brain samples from persons at potentially pre-symptomatic or a-symptomatic stages of AD, which contain substantial cerebral amyloid deposits, but not overt dementia. In the present study, we evaluated the Aβ seeding capability of MCI and NDAN brains in AD-transgenic animals. Strikingly, we found that MCI and NDAN samples can exacerbate amyloid deposition to a similar or even greater extent than AD specimens.

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