Selective loss of nigral neurons in Alzheimer's disease: a morphometric study

Loss of neurons from the substantia nigra (SN), which is sometimes observed in Alzheimer's disease (AD), was quantitatively analyzed in 10 cases of presenile AD and 19 age-matched controls. On sections from the upper and lower portions of the SN, the pigmented zone (zona compacta) and the non-pigmented zone (zona reticulata) were delineated, and these zones were partitioned into quarters: medial, mid-medial, mid-lateral and lateral. This approach clarified topographical preference of neuronal depletion in the SN of AD; namely (1) pigmented neurons were more severely affected than non-pigmented neurons, (2) neuronal depletion was more marked in the lower SN (-38%, P less than 0.001), where the pigmented neurons in the medial quarter were most severely affected (-51%, P less than 0.001), (3) in the upper SN (neuronal loss: -21%, P less than 0.01), the pigmented neurons in the mid-medial quarter were most severely affected (-43%, P less than 0.01). These findings suggest that some groups of nigral neurons are primarily involved in presenile AD. Gallyas staining after bleaching of melanin pigments uncovered a large number of neurofibrillary tangles (NFTs) mainly in the pigmented zone, especially in the medial quarter. A large number of NFTs, scarse senile plaques, and substantial depletion of neurons form an unique combination of Alzheimer pathology in the SN not well recognized so far.