Abstract
Dystrophic neurites (DNs) are found in many neurological conditions such as traumatic brain injury and age-related neurodegenerative diseases. In Alzheimer’s disease (AD) specifically, senile plaques containing silver-stained DNs were already described in the original literature defining this disease. These DNs could be both axonal and dendritic in origin, while axonal dystrophy relative to plaque formation has been more extensively studied. Here, we demonstrate an early occurrence of dendritic dystrophy in the hippocampal CA1 and subicular regions in human brains (n = 23) with primary age-related tauopathy (PART), with neurofibrillary tangle (NFT) burden ranging from Braak stages I to III in the absence of cerebral β-amyloid (Aβ) deposition. In Bielschowsky’s silver stain, segmented fusiform swellings on the apical dendrites of hippocampal and subicular pyramidal neurons were observed in all the cases, primarily over the stratum radiatum (s.r.). The numbers of silver-stained neuronal somata and dendritic swellings counted over CA1 to subiculum were positively correlated among the cases. Swollen dendritic processes were also detected in sections immunolabeled for phosphorylated tau (pTau) and sortilin. In aged and AD brains with both Aβ and pTau pathologies, silver- and immunolabeled dystrophic-like dendritic profiles occurred around and within individual neuritic plaques. These findings implicate that dendritic dystrophy can occur among hippocampal pyramidal neurons in human brains with PART. Therefore, as with the case of axonal dystrophy reported in literature, dendritic dystrophy can develop prior to Alzheimer-type plaque and tangle formation in the human brain.
Highlights
Malformations of axonal or dendritic processes are generally referred to as neuritic pathology
We demonstrate an early occurrence of dendritic dystrophy in the hippocampal CA1 and subicular regions in human brains (n = 23) with primary age-related tauopathy (PART), with neurofibrillary tangle (NFT) burden ranging from Braak stages I to III in the absence of cerebral β-amyloid (Aβ) deposition
There were 12 cases that exhibited Braak stage II neuropathology, with phosphorylated tau (pTau)-labeled pyramidal neurons present in the hippocampal CA1 sector, with a few neurons occasionally seen in the parahippocampal gyrus (PHG) at high magnification (Figures 1G–J)
Summary
Malformations of axonal or dendritic processes are generally referred to as neuritic pathology. The silver-stained senile plaques observed in the brains of non-demented and demented elderly over a century ago were shown to consist of some extracellular amorphous substance and swollen neuritic structures (Critchley, 1929; García-Marín et al, 2007; Ohry and Buda, 2015). The former was further found to be amylophilic (i.e., binding to such as Congo red and thioflavin) and related to the peptides named as β-amyloid (Aβ; Oifa, 1973; Glenner and Wong, 1984; Coria et al, 1988). The plaque-associated neurites were called dystrophic neurites (DNs), as their precise origin from axons or dendrites was initially not clear about
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