Huntingtin in the amygdaloid basolateral complex is correlated with Vonsattel staging in Huntington’s disease

TL;DR

Huntingtin deposits in a brain region called the amygdaloid basolateral complex are linked to disease severity in Huntington’s disease and may explain nonmotor symptoms like depression.

Contribution

The study identifies a correlation between huntingtin deposits in the amygdala and Vonsattel staging, offering new insights into nonmotor symptoms and neuropathological diagnosis.

Findings

Huntingtin deposits in the amygdaloid basolateral complex correlate with Vonsattel neuropathological grades.

Huntingtin deposits are not influenced by sex or CAG repeat length but are associated with nonmotor symptoms like depression.

Other proteinopathies coexist with huntingtin aggregates in the amygdala.

Abstract

Huntington’s disease has traditionally been considered a motor disorder, but it is currently classified as a multisystem neurodegenerative disease that involves brain regions, such as the amygdala, and causes depression. The aim of the present study was to analyse the distribution of huntingtin in the human amygdaloid basolateral complex, considering its nuclei, sex, triplet repeats and Vonsattel score, as well as to characterize the cellular relationships between huntingtin and associated copathologies. The present study included 23 human brain samples from patients (males and females) with and without Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. An unbiased stereology approach was used to quantify huntingtin deposits. Multiple immunofluorescence experiments were conducted to analyse the relationship between huntingtin and glial populations. Immunohistochemistry against pathological markers of other neurodegenerative diseases was also carried out. Quantification data did not reveal differences among different nuclei (basomedial, basolateral or lateral) in the basolateral complex or according to sex. Huntingtin deposits did not correlate with cytosine–adenine–guanine (CAG) repeats. However, these deposits were positively correlated with pathological Vonsattel grades. Additional aggregates of other pathological proteinopathies were also observed. This correlation between the human basolateral amygdaloid complex and the Vonsattel stage provides a new perspective for neuropathological diagnosis and helps in understanding nonmotor symptoms such as depression.

Sanchez-Migallon et al. report that huntingtin deposits in the human amygdaloid basolateral complex positively correlate with Vonsattel neuropathological grades. This provides a new perspective for neuropathological diagnosis and helps in understanding nonmotor symptoms such as depression.

Graphical Abstract

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