Tau protein aggregation in the frontal and entorhinal cortices as a function of aging.

OBJECTIVES

The abnormal accumulation of tau protein is increasingly recognized as the neuropathological hallmark of a number of dementing illness in which frontotemporal lobar degeneration occurs. In this paper we examined the age-dependant deposition of tau protein in the frontal and entorhinal neocortices.

METHODS

We examined autopsy records from 1997 to 2002 and selected 87 cases (10 in each decade from 0 to 79 years of age, 7 in 80-89 decade) with no history of dementia or other neurodegenerative diseases, and for which neurodegenerative diseases were excluded neuropathologically. Archival paraffin-embedded frontal and entorhinal cortices were examined by both Gallyas-Braak silver staining and a panel of antibodies recognizing tau protein accumulation.

RESULTS

Tau neuronal aggregates were observed in both frontal and entorhinal cortices in the third decade. While the frontal neuronal tau aggregates remained infrequent in the remaining decades, the number and extent ofneuronal tau aggregates in the entorhinal cortex increased such that by the 7th decade the majority of cases showed extensive tau aggregate formation. The most consistent morphological observation was of dense, perikaryal neuronal tau-immunoreactive aggregates, similar to the total tau distribution, firstly presenting in cortical layers II and III and subsequently involving in layers IV-VI. Neuropil threads became maximal in the 9th decade in both frontal and entorhinal cortices. Astrocytic tau accumulation was first observed in both frontal and entorhinal cortices in the 6th decade, predominantly in layer I and subcortical white matter, and increased in number with aging. Extraneuronal tau reactive aggregates and coiled bodies were rarely observed in the entorhinal cortex, and when present, were scattered through layer II to VI.

CONCLUSIONS

We have observed an age-dependant pattern of neuronal, extraneuronal and glial tau protein accumulation in the entorhinal cortex in individuals without neurodegenerative diseases. In contrast, tau protein aggregation is infrequently observed in the frontal cortex as a function of aging.