# Neurodegeneration Within the Spectrum of Pervasive Developmental Disorders

## TL;DR

This paper explores how neurodevelopmental disorders like autism may share mechanisms with neurodegenerative diseases, suggesting a need for integrated approaches to long-term neurological health.

## Contribution

The paper introduces a novel integrative model linking developmental and degenerative processes in pervasive developmental disorders.

## Key findings

- Shared biological pathways like synaptic pruning and mitochondrial dysfunction link neurodevelopmental and neurodegenerative processes.
- Conditions like Rett syndrome exemplify the overlap between developmental and degenerative neurological disorders.
- Longitudinal data gaps hinder understanding of aging risks in individuals with autism spectrum disorder.

## Abstract

The historical framework of pervasive developmental disorders (PDD) continues to hold relevance despite its replacement by the Neurodevelopmental Disorders category in DSM-5. Emerging evidence indicates that neurodevelopmental and neurodegenerative mechanisms, traditionally considered distinct, may intersect in individuals formerly classified under PDD. Shared biological pathways, including aberrant synaptic pruning, mitochondrial dysfunction, immune dysregulation, and impaired proteostasis, suggest potential long-term neurological vulnerability, particularly in autism spectrum disorder (ASD), the principal diagnosis within the former PDD group. Clinical overlap is most evident in "bridging conditions" such as Rett syndrome, MECP2-related disorders, and Fragile X-associated tremor/ataxia syndrome, which illustrate the continuum between developmental and degenerative processes. As individuals with ASD increasingly reach older adulthood, gaps in longitudinal data hinder understanding of risks related to cognitive decline, dementia, and atypical aging. Additionally, chronic stress, psychiatric comorbidities, and sensory dysregulation may further influence neuroinflammatory and neurodegenerative pathways. Recognizing these intersections provides opportunities for early neuroprotective interventions and biomarker-driven risk stratification. This editorial argues for a lifespan-oriented, integrative model that bridges developmental and degenerative neuroscience, aiming to better characterize and support the long-term neurological health of individuals previously encompassed by the PDD construct.